Process for recovering pertechnetate ions from an aqueous solution also containing other ions

ABSTRACT

A solid/liquid process for the separation and recovery of TcO 4   -1  ions from an aqueous solution is disclosed. The solid support comprises separation particles having surface-bonded poly(ethylene glycol) groups; whereas the aqueous solution from which the TcO 4   -1  ions are separated contains a poly(ethylene glycol) liquid/liquid biphase-forming amount of a dissolved salt. A solid/liquid phase admixture of separation particles containing bound TcO 4   -1  ions in such an aqueous solution that is free from MoO 4   -2  ions is also contemplated, as is a chromatography apparatus containing that solid/liquid phase admixture.

GOVERNMENTAL SUPPORT AND RIGHTS

This invention was made with government support pursuant to Contract No.W-31-109-ENG-38 between the U.S. Department of Energy and The Universityof Chicago, contractor for Argonne National Laboratory. The Governmenthas certain rights in this invention.

TECHNICAL FIELD

The present invention relates to the separation and recovery ofpertechnetate ions (TcO₄ ⁻¹) from aqueous solutions and moreparticularly to the separation and recovery of pertechnetate compoundsfrom aqueous solutions that contain salts of other elements such asradioactive molybdate in a solid/liquid separation process such as achromatographic process, as well as an aqueous admixture containing TcO₄⁻¹ ion-bound particles and a chromatographic apparatus containingseparated, bound pertechnetate ions.

BACKGROUND ART

Solid support-based chromatographic methods have been extensivelyapplied in separation science for many years. [Harris, QuantitativeChemical Analysis, 2nd ed., W. H. Freeman and Co., New York (1987);Skoog, Principles of Instrumental Analysis, 3rd ed., Saunders CollegePublishing, New York (1985); Giddings, Unified Separation Science, JohnWiley & Sons, New York, (1991)] Excellent chemical separations can beachieved due to the inherent variables of solid/liquid chromatography[Skoog, Principles of Instrumental Analysis, 3rd, ed., Saunders CollegePublishing, New York (1985)] that include the ability to vary both thesupport material and mobile phase. Several advantages over solventextraction include the immobilization of the extractant and the absence(or decreased need in the case of extraction chromatography) of organicsolvent diluents. As for solvent extraction, scale-up of solidsupport-based chromatographic methods is feasible with the major concernof the pressure drop across a large column balanced by the simplicity ofthe chromatographic apparatus versus liquid/liquid contactor apparatus.

Due to the rich history of liquid/liquid aqueous biphasic separationsfor biological separations, [Poly(Ethylene Glycol) Chemistry:Biotechnical and Biomedical Applications; Harris, ed., Plenum Press, NewYork (1992); Aqueous Two-Phase Systems, Walter and Johansson, eds., inMethods in Enzymology, Academic Press, San Diego, Vol. 228 (1994);Albertsson, Partition of Cell Particles and Macromolecules, 3rd ed.,John Wiley & Sons, New York (1986); Partitioning in Aqueous Two-PhaseSystems. Theory, Methods, Uses and Applications to Biotechnology,Walter, Brooks and Fisher, eds., Academic Press, Orlando (1991)] work onsolid-supported biphasic separations has focused on biological species.No work has been reported in the area of aqueous biphasic partitioningof metal ions using solid support separation particles.

The chelation properties of solid-supported short chain polyethers havebeen investigated, but the mobile phases were largely aqueous acids andthe systems lacked genuine aqueous biphasic behavior. The chelationproperties of the high molecular weight poly(ethylene glycols) (PEGs) isgenerally perceived to be quite low. Consequently, high molecular weightPEG resins have not been investigated for ion separations.

The major variables influencing liquid/liquid aqueous biphasicseparations, type and concentration of polymers and salt and polymermolecular weight, are important variables to consider in the design ofaqueous biphasic chromatographic materials. The current focus is onmetal ion separations from solutions of high ionic strength because mostmetal-containing waste streams have relatively high concentrations ofmatrix ions.

Two major drawbacks to aqueous biphasic separations operating in theliquid/liquid mode are loss of the phase-forming components, PEG orsalt, due to their high solubilities in water and the difficulty instripping partitioned solutes. Because high concentrations of thephase-forming components are required to sustain a two-phase system, anyloss of PEG or salt is of concern. In addition, different concentrationsof phase-forming components have been shown to affect metal iondistribution ratios in liquid/liquid systems. [Rogers et al., SolventExtr. Ion Exch., (in press 1995); Rogers et al., Aqueous BiphasicSeparations: Biomolecules to Metal Ions, (in press 1995)]

More importantly, once the solute of interest has been partitioned tothe upper PEG-rich phase of an aqueous liquid/liquid biphase, itsisolation from this matrix has proven to be difficult. The backextraction conditions vary from chemical destruction of the extractantand partitioned complex to chemical reduction of the partitioned species[pertechnetate reduction by tin(II) chloride]. [Rogers et al., SolventExtr. Ion Exch., (in press 1995); Rogers et al., Aqueous BiphasicSeparations: Biomolecules to Metal Ions, (in press 1995)]

Polyethylene glycols have been bound to a variety of differentmaterials, with the choice of support based primarily on the desiredapplication. Solid-supported short chain PEGs have been grafted toStyrene-based resins for use as phase transfer catalysts in organicsynthesis, [Regen et al., J. Am. Chem. Soc., 101:116 (1979); Yanagida etal., J. Org. Chem., 44:1099 (1979); Fukunishi et al., J. Org. Chem.,46:1218 (1981); Heffernan et al., J. Chem. Soc., Perkin Trans.2:514(1981); Kimura et al., Synth. Commun., 13:443 (1983); Kimura et al., J.Org. Chem., 48:195 (1983)] and to urethane foams to act as potentialmetal ion chelators. [Jones et al., Anal. Chim. Acta, 182:61 (1986);Fong et al., Talanta, 39:825 (1992)] Polyethers have also been bound tovarious surfaces to decrease protein adhesion in biomedical applications[Nagaoka et al., Antithrombogenic Biomedical Material, Toray Industries,Inc. (1983); Toyobo Co., Antithrombogenic Membranes, Toyobo Co. (1983)]and medium weight PEGs have been fused to silica capillaries for avariety of separations. [Nashabeh et al., J. Chromatogr., 559:367(1991); Herren et al., J. Coll. Interf. Sci., 115:46 (1987)] Highmolecular weight PEGs have been bound to silica [Matsumoto et al., J.Chromatogr., 187:351 (1980)] and Sepharose [Matsumoto et al., J.Chromatogr., 187:351 (1980); Matsumoto et al., J. Chromatogr., 268:375(1981); Matsumoto et al., J. Chromatogr., 285:69 (1984)] primarily forpolymer/polymer separations of biomolecules. Two recent reviews of PEGchemistry also point to the utility of solid-supported PEGs forbioanalytical separations. [Poly(Ethylene Glycol) Chemistry:Biotechnical and Biomedical Applications, Harris ed., Plenum Press, NewYork (1992); Aqueous Two-Phase Systems, Walter et al., eds., in Methodsin Enzymology Academic Press, San Diego, 228 (1994)] Each of thepreviously mentioned materials served as chelators or hydrophiliccoatings to promote or inhibit different types of adsorption processes.

The importance of ^(99m) Tc in nuclear medicine and the problemsassociated with disposal of ⁹⁹ Tc in nuclear waste require new andbetter separations technologies for this element. In radiopharmacy, theshort-lived ^(99m) Tc (t_(1/2) =6 hours) that decays to ⁹⁹ Tc (t_(1/2)=2.12×10⁵ years), is used in the vast majority of all medical proceduresutilizing radioisotopes. [Boyd, Radiochim. Acta, 30:123 (1982);Steigman, The Chemistry of Technetium in Medicine, National AcademyPress, Washington, D.C. (1992)]

One of the more common ways to access ^(99m) Tc is by eluting thepertechnetate ion (TcO₄ ⁻¹) from an alumina column containing ⁹⁹ MoO₄ ⁻²ion (t_(1/2) =66.7 hours), itself obtained by neutron activationirradiation of ⁹⁸ Mo or as a ²³⁵ U fission product. So-called "instanttechnetium" involves the solvent extraction of ^(99m) TcO₄ ⁻¹ from analkaline solution of Na₂ ⁹⁹ MoO₄ using methyl ethyl ketone. Both methodssuffer disadvantages including the presence of organic impurities andlow radiochemical yield. [Boyd, Radiochim. Acta, 30:123 (1982);Steigman, The Chemistry of Technetium in Medicine, National AcademyPress, Washington, D.C. (1992); Lamson et al., J. Nucl. Med., 16:639(1975); Nair et al., Radiochim. Acta, 57:29 (1992)]

Relatively high levels of ⁹⁹ TcO₄ ⁻¹ are present in the highly alkalinewaste storage tanks at Westinghouse Hanford [Fong et al., Talanta,39:825 (1992)] and Savannah River [Walker et al., Mat. Res. Soc. Symp.Proc., 44:805 (1985)], among others. Technetium-99 is a fission productin nuclear fuel burn-up. Its long half life and its environmentalmobility (as TcO₄ ⁻¹) present long term storage problems [Mobius, et al, "Gmelin Handbook of Inorganic Chemistry, Tc, Technetium: Metal Allgys,Compounds, Chemistry in Solution", 8th ed Supplemental vol 2 p 243Kugler & Kellar, eds., Springer-Verlag, Berlin (1983); Jones,"Comprehensive Coordination Chemistry", Vol 6 p 881, Wilkinson et al.,eds., Pergamon Press, Oxford (1987)]

Current extraction technologies for Tc run the gamut from solventextraction to ion exchange in batch and chromatographic separations, andprecipitation reactions. [Mobius, et al., "Gmelin Handbook of InorganicChemistry, Tc, Technetium: Metal Alloys, Compounds, Chemistry inSolution", 8th ed., Supplemental vol. 2, p. 243, Kugler & Kellar, eds.,Springer-Verlag, Berlin (1983)] The synthetic organic reagents or resinsused are often subject to radiation damage (in high level nuclear wasteapplications) and large cations (e.g., UO₂ ⁺², Zr⁺⁴) can be coextracted.[Mobius, et al., "Gmelin Handbook of Inorganic Chemistry, Tc,Technetium: Metal Alloys, Compounds, Chemistry in Solution", 8th ed.,Supplemental vol. 2, p. 243, Kugler & Kellar, eds., Springer-Verlag,Berlin (1983); Jassim et al., Solvent Extr. Ion Exch., 2:405 (1984);Kolarik et al., Solvent Extr. Ion Exch., 7:625 (1989)] New separationstechniques and tailored waste forms are needed for selective removal andimmobilization of ⁹⁹ Tc.

The pertechnetate ion partitions to the polymer-rich phase inliquid/liquid PEG-based aqueous biphasic systems from a variety of saltsolutions including OH⁻¹, CO₃ ⁻², SO₄ ⁻² and PO₄ ⁻³. Increasing theincompatibility between the two phases forces more of the TcO₄ ⁻¹ intothe PEG-rich phase. This can be accomplished either by increasing thesalt concentration or increasing the PEG-2000 concentration from about20 weight percent to about 70 weight percent of the aqueous solution.

It would therefore be beneficial if the selective binding of TcO₄ ⁻¹ions to PEG resins found in aqueous hipbasic separations could beadapted to a solid support-based separation and recovery process, whileat the same time, overcoming the problems inherent in recovering theTcO₄ ⁻¹ ions from an aqueous bipbasic separation system using a solidphase that is not adversely affected by radiation present. Thediscussion that follows provides one solution to the TcO₄ ⁻¹ recoveryproblem.

BRIEF SUMMARY OF THE INVENTION

The present invention relates to a separation and recovery process thateffectively separates and recovers TcO₄ ⁻¹ ions from an aqueous solutioncontaining other ions such as MoO₄ ⁻² ions, as well as an aqueousadmixture containing TcO₄ ⁻¹ ion-bound particles and a chromatographyapparatus containing separated, bound pertechnetate ions.

In one embodiment, a process for recovering TcO₄ ⁻¹ ions from an aqueoussolution is contemplated. That process comprises the steps of:

(a) contacting separation particles with an aqueous solution containing(i) TcO₄ ⁻¹ ions and (ii) a poly(ethylene glycol) liquid/liquidbiphase-forming amount of a dissolved salt to form a solid/liquid phaseadmixture. The separation particles comprise particles having aplurality of covalently bonded --X--(CH₂ CH₂ O)_(n) --CH₂ CH₂ R groupswherein X is O, S, NH or N--(CH₂ CH₂ O)_(m) --R³ where m is a numberhaving an average value of zero to about 225, n is a number having anaverage value of about 15 to about 225, R³ is hydrogen, C₁ -C₂ alkyl,2-hydroxyethyl or CH₂ CH₂ R, and R is selected from the group consistingof --OH, C₁ -C₁₀ hydrocarbyl ether having a molecular weight up to aboutone-tenth that of the --(CH₂ CH₂ O)_(n) -- portion, carboxylate,sulfonate, phosphonate and --NR¹ R² groups where each of R¹ and R² isindependently hydrogen, C₂ -C₃ hydroxyalkyl or C₁ -C₆ alkyl, or --NR¹ R²together form a 5- or 6-membered cyclic amine having zero or one oxygenatom or zero or one additional nitrogen atom in the ring. The separationparticles having a percent CH₂ O/mm² of particle surface area of greaterthan about 8000 and less than about 1,000,000.

(b) That contact is maintained for a time period sufficient to form TcO₄⁻¹ ion-bound separation particles and an aqueous solution substantiallyfree of TcO₄ ⁻¹ ions.

(c) The TcO₄ ⁻¹ ion-bound separation particles are contacted with asecond aqueous solution that does not contain a poly(ethylene glycol)liquid/liquid biphase-forming amount of dissolved salt to free the TcO₄⁻¹ ions from the separation particles and form an aqueous solutioncontaining free TcO₄ ⁻¹ ions.

(d) The free TcO₄ ⁻¹ ion-containing aqueous solution is then recovered.

In preferred practice, the TcO₄ ⁻¹ ion-bound separation particles (solidphase) are separated from the aqueous solution (liquid phase) of step(b) in the presence of an aqueous solution of a poly(ethylene glycol)liquid/liquid biphase-forming amount of a salt to form a secondsolid/liquid phase admixture containing TcO₄ ⁻¹ ion-bound separationparticles.

In another embodiment including the before-discussed preferred addedstep after step (b), a process is contemplated for recovering TcO₄ ⁻¹ions from an aqueous solution containing TcO₄ ⁻¹ and MoO₄ ⁻² ions. Thatprocess comprises the steps of:

(a) contacting separation particles as described before with an aqueoussolution containing (i) TcO₄ ⁻¹ ions, (ii) MoO₄ ⁻² ions and (iii) apoly(ethylene glycol) liquid/liquid biphase-forming amount of adissolved salt whose anions can include MoO₄ ⁻² ions to form asolid/liquid phase admixture.

(b) That contact is maintained for a time period sufficient to form TcO₄⁻¹ ion-bound separation particles and an aqueous solution substantiallyfree of TcO₄ ⁻¹ ions, thereby separating the TcO₄ ⁻¹ ions from the MoO₄⁻² ions. The MoO₄ ⁻² ion-containing aqueous solution so formed is thussubstantially free of TcO₄ ⁻¹ ions, except for newly generated TcO₄ ⁻¹ions that can form from radioactive MoO₄ ⁻² present in that solution.

(c) The TcO₄ ⁻¹ ion-bound separation particles (solid phase) areseparated from the aqueous solution (liquid phase) of step (b) in thepresence of a second aqueous solution of a poly(ethylene glycol)liquid/liquid biphase-forming amount of a salt free of MoO₄ ⁻² ions toform a second solid/liquid phase admixture containing TcO₄ ⁻¹ ion-boundseparation particles.

(d) The TcO₄ ⁻¹ ion-bound separation particles of step (c) are contactedwith an aqueous solution that does not contain a poly(ethylene glycol)liquid/liquid biphase-forming amount of salt to free the TcO₄ ⁻¹ ionsfrom the separation particles and form an aqueous solution containingfree TcO₄ ⁻¹ ions.

(e) The free TcO₄ ⁻¹ ion-containing aqueous solution is then recovered.

The TcO₄ ⁻¹ ions bound and recovered in this process are preferably^(99m) TcO₄ ⁻¹ ions and the MoO₄ ⁻² ions of the various aqueoussolutions are radioactive, and are preferably ⁹⁹ MoO₄ ⁻² ions. The CH₂O/mm² value is preferably greater than about 9,000 and less than about20,000, and R is preferably C₁ -C₆ alkyl, and most preferably methyl.

Still another embodiment of the invention contemplates a solid/liquidphase admixture that comprises TcO₄ ⁻¹ ion-bound separation particles asthe solid phase in an aqueous solution of a poly(ethylene glycol)liquid/liquid biphase-forming amount of a dissolved salt that is free ofMoO₄ ⁻² ions. The separation particles are as discussed before. Acontemplated solid/liquid phase admixture is particularly useful withina chromatography column as part of a chromatography apparatus.

The above-mentioned preferences noted for the process apply also to thesolid/liquid phase admixture and chromatography apparatus.

BRIEF DESCRIPTION OF THE DRAWINGS

In the drawings forming a portion of this disclosure,

FIG. 1 is a graph of D_(w) values for TcO₄ ⁻¹ ions versus the molalityof several salts using 107-350 particles at 25° C. Here, data obtainedusing (NH₄)₂ SO₄ as the liquid/liquid biphase-forming salt are shown asdarkened squares, those obtained using NaOH as the biphase former areshown as stars, those obtained using K₂ CO₃ as the biphase former areshown using darkened diamonds, and those obtained using K₃ PO₄ as thebiphase former are shown using darkened circles.

FIG. 2 is a graph similar to the graph of FIG. 1 using 107-750separation particles. Data are presented as in FIG. 1 except that dataobtained using K₃ PO₄ are shown as darkened squares and those obtainedusing (NH₄)₂ SO₄ are shown as darkened circles.

FIG. 3 is a graph similar to the graph of FIG. 2 using 107-2000separation particles. Data obtained using the four salts are shown as inFIG. 2.

FIG. 4 is a graph similar to the graph of FIG. 2 using 107-5000separation particles. Data obtained using the four salts are shown as inFIG. 2.

FIG. 5 is a graph of D_(w) values for TcO₄ ⁻¹ ions versus the molalityof (NH₄)₂ SO₄ on the abscissa using four separation particle types at25° C. Data for 107-5000 separation particles are shown as stars, datafor 107-2000 separation particles are shown as darkened squares, datafor 107-750 separation particles are shown as darkened diamonds, anddata for 107-350 separation particles are shown as darkened circles.

FIG. 6 is a graph similar to that of FIG. 5 except that molality of K₂CO₃ is shown on the abscissa.

FIG. 7 is a graph similar to that of FIG. 5 except that molality of K₂PO₄ is shown on the abscissa.

FIG. 8 is a graph similar to that of FIG. 5 except that molality of NaOHis shown on the abscissa.

FIG. 9 is a graph of D or D_(w) values at 25° C. for TcO₄ ⁻¹ ions using107-2000 particles in K₂ CO₃ (darkened diamonds) and (NH₄)₂ SO₄(darkened circles) and liquid/liquid biphase extraction using PEG-2000in K₂ CO₃ (stars) and (NH₄)₂ SO₄ (darkened squares) plotted versus saltmolality.

FIG. 10 shows D_(w) values for TcO₄ ⁻¹ ions at 25° C. versus themolecular weight of poly(ethylene glycol) methyl ether used to prepare107-350 particles or 107-750, -2000 and -5000 separation particles fromthree simulated Hanford Tank Wastes: SY-101 (darkened circles) NCAW(darkened squares) and SST (darkened diamonds).

FIG. 11 shows the results of a separation and recovery process describedherein using 107-5000 separation particles at 22° C. Counts per minuteper milliliter (cpm/mL) with the exponent shown are plotted on theordinate for ⁹⁹ MoO₄ ⁻² (open circles) and ^(99m) TcO₄ ⁻¹ (opensquares). Free column volumes (fcv) of eluate are plotted on theabscissa.. The column was loaded for about 29 fcv with 5M NaOH,thereafter washed with 3M K₂ CO₃ for about 13 fcv and then strippedusing water for about another 34.5 fcv. The column had a fcv of 0.392mL.

FIG. 12 is another graph of the process whose results are shown in FIG.11 but using a broken axis as the ordinate.

FIG. 13 is a graph showing D_(w) values for TcO₄ ⁻¹ ions in 2.0M (2.3 m)(NH₄)₂ SO₄ at 25° C. using 107-5000 separation particles in the absence(darkened square) and presence of various molal concentrations of NH₄ReO₄ (darkened circles).

FIG. 14 is a graph showing D_(w) values for TcO₄ ⁻¹ ions in 5.9 m K₂ CO₃at 25° C. versus percent CH₂ O/mm² of particle surface for variousparticles. Those particles were: Merrifield's peptide resin used herein(darkened circle); 107-350 (darkened square); 107-750 separationparticles (darkened triangle); 107-2000 separation particles (darkenedinverted triangle); 107-5000 separation particles (darkened diamond) and107-5750 separation particles (darkened hexagon).

FIG. 15 is a graph showing D_(w) values for TcO₄ ⁻¹ ions at 25° C. using107-5000 separation particles that had been irradiated with 1.2 Mrads inwater (open boxes) or 5M NaOH (inverted triangles), irradiated with 12Mrads in. water (open hexagons) and irradiated with 24 Mrads in water(triangle plus cross) or 5M NaOH (diamond plus cross) compared tounirradiated particles (darkened circles) as a function of K₂ CO₃concentration. Data are shown as in FIG. 5.

DETAILED DESCRIPTION OF THE INVENTION

It has now been found that the benefits of PEG-induced TcO₄ ⁻¹separations observed in liquid/liquid separations can be had in a solidsupport-based solid/liquid phase separation process in which particularPEGs are bonded to solid particles. It has also surprisingly been foundthat the separated TcO₄ ⁻¹ ions can be readily recovered from thesolid-supported PEG resin, thereby overcoming the major drawback of theliquid/liquid separation process. Still more surprising is the fact thatthe distribution factor for separated pertechnetate ions, D_(w), can beabout an order of magnitude or more greater in the solid/liquid phaseprocess than in the liquid/liquid process. In addition, radiation damageto the solid support after several separation and recovery procedures isminimal to being undetectable.

The Process

In accordance with a process aspect of this invention, recovery of TcO₄⁻¹ ions from an aqueous solution containing TcO₄ ⁻¹ and other anionssuch as MoO₄ ⁻² ions is contemplated. A process where MoO₄ ⁻² ions arepresent is discussed first, followed by a more general process. Theprocess where both TcO₄ ⁻¹ and MoO₄ ⁻² ions are present comprises thesteps of:

(a) contacting separation particles with an aqueous solution containing(i) TcO₄ ⁻¹ ions, (ii) MoO₄ ⁻² ions and (iii) a poly(ethylene glycol)liquid/liquid biphase-forming amount of a dissolved salt whose anionscan include MoO₄ ⁻² ions to form a solid/liquid phase admixture. Theseparation particles comprise particles having a plurality of covalentlybonded surface --X--(CH₂ CH₂ O)_(n) --CH₂ CH₂ R groups wherein X is O,S, NH or N--(CH₂ CH₂ O)_(m) --R³, wherein m is a number having anaverage value of zero to about 225, n is a number having an averagevalue of about 15 to about 225, R³ is hydrogen, C₁ -C₂ alkyl,2-hydroxyethyl or CH₂ CH₂ R, and R is selected from the group consistingof --OH, C₁ -C₁₀ hydrocarbyl ether having a molecular weight up to aboutone-third that of the --(CH₂ CH₂ O)_(n) -portion, carboxylate,sulfonate, phosphonate and --NR¹ R² groups where each of R¹ and R² isindependently hydrogen, C₁ -C₆ alkyl or C₂ -C₃ hydroxyalkyl, or --NR¹ R²together form a 5- or 6-membered cyclic amine having zero or one oxygenatom or zero or one additional nitrogen atom in the ring. The separationparticles have a percent CH₂ O/mm² of particle surface area of greaterthan about 8000 and less than about 1,000,000.

(b) That contact is maintained for a time period sufficient to form TcO₄⁻¹ ion-bound separation particles and an aqueous solution containingMoO₄ ⁻² ions, thereby separating TcO₄ ⁻¹ ions from MoO₄ ⁻² ions. TheMoO₄ ⁻² ion-containing aqueous solution thus has a reduced concentrationof TcO₄ ⁻¹ ions, that reduction is preferably to zero TcO₄ ⁻¹ ionsexcept for newly generated TcO₄ ⁻¹ ions that can form from MoO₄ ⁻² ionsby radioactive decay.

(c) The TcO₄ ⁻¹ ion-bound separation particles are then preferablyseparated from the aqueous solution of step (b) in the presence of anaqueous solution of a poly(ethylene glycol) liquid/liquidbiphase-forming amount of a salt to form a second solid/liquid phaseadmixture containing TcO₄ ⁻¹ ion-bound separation particles That aqueoussolution is free of MoO₄ ⁻² ions

(d) The TcO₄ ⁻¹ ion-bound separation particles of step (b) or (c) arecontacted with a second aqueous solution that does not contain apoly(ethylene glycol). liquid/liquid biphase-forming amount of salt tofree the TcO₄ ⁻¹ ions from the separation particles and form an aqueoussolution containing free TcO₄ ⁻¹ ions.

(e) The free TcO₄ ⁻¹ ion-containing aqueous solution is then recovered.

Turning more specifically to the process and its constituent materialsand manipulations, one notes that separation particles are utilized.These separation particles are particles that are hydrophilic andinclude poly(ethylene glycol) groups of a particular length andtherefore molecular weight as is discussed hereinafter.

The particles can be quite varied in make-up, and are inert to andinsoluble in the separation/recovery aqueous salt biphase-formingenvironment that can be very acidic or basic. Exemplary preferredparticles are the particularly preferred reacted cross-linkedpoly(styrene-vinyl benzyl halide) resins often called Merrifield'speptide resin or chloromethylated divinylbenzene cross-linkedpolystyrene, as well as glass or silica gel (silica-based) materials,cross-linked poly(ethylene glycol)-containing urethane or urea resins,cross-linked dextran- and agarose-based materials, and also variouscross-linked acrylate esters.

It is noted that the separation particles can contain some reactivefunctionality such as benzyl halide groups that can react in the aqueousbiphase-forming environment. However, any such reaction is minimal anddoes not alter the properties of the separation particles. Suchseparation particles are then deemed to be "inert" to their environmentfor the purpose of a separation and recovery as described herein.

As noted before, the cross-linked, styrene-based Merrifield's peptideresins are particularly preferred. These materials are available from anumber of commercial sources such as Sigma Chemical Co., St. Louis, Mo.in several sizes and having differing amounts of cross-linking anddiffering amounts of replaceable chloride ion. The preparation ofexemplary resins is also detailed hereinafter. Preferred commerciallyavailable materials are 200-400 mesh particles that contain about0.4-0.9 meq chlorine/gram or about 0.9-1.5 meq chlorine/gram at onepercent cross-linking and a material containing about 1 meqchlorine/gram at two percent cross-linking.

Merrifield's peptide resin particles are readily transformed intoseparation particles by reaction in a solvent inert to the reactionconditions with an alkali metal salt of a desired long chain PEGcompound, followed by rinsing to remove any unreacted materials and thealkali metal halide reaction product. The PEG-containing separationparticles are therefore referred to as "reacted".

A Merrifield's peptide resin can also first be reacted with a shorterPEG compound such as tetraethylene glycol followed by reaction withethylene oxide to extend the chains. One such synthetic process isdescribed in Bayer et al., Poly(Ethylene Glycol) Chemistry: Biotechnicaland Biomedical Applications, Harris ed., Plenum Press, New York (1992)p. 325. A similar reaction can be carried out using an alkanol aminesuch as mono- or diethanolamine followed by a chain lengthening reactionwith ethylene oxide. An aminomethyl Merrifield's peptide resin (Sigma)can similarly be reacted with ethylene. oxide to form desired,amine-containing separation particles. Similar reactions using sodiumsulfide and then ethylene oxide or 2-mercaptoethanol and then ethyleneoxide can be used to form sulfur-containing separation particles.

Another group of solid support particles are cross-linked acrylicesters, particularly those having about 60 to about 98 weight percentglycidyl methacrylate with the remaining amount of monomer beingcross-linking agent, and methyl methacrylate. Methyl methacrylate atabout 68 to about 48 weight percent, a cross-linker and about 30 toabout 50 weight percent of a PEG-750 to -5000 methacrylate ester whosePEG portion has a formula --O--(CH₂ CH₂ O)_(n) --CH₂ CH₂ R as isdiscussed hereinafter can also be copolymerized.

Exemplary cross-linking agents for acrylate-based particles includetrimethylolpropane trimethacrylate[2-ethyl-2(2-hydroxymethyl)-1,3-propanediol trimethacrylate],pentaerythritol triacrylate and the like as are well known. Across-linking agent is typically used at about 1 to about 5 weightpercent and more preferably at about 2 to about 4 weight percent of themonomer mixture.

Support particles containing polymerized glycidyl methacrylate repeatingunits are post-reacted with an appropriate PEG compound to open theepoxy ring to form an ester-linked hydroxy-ether separation particle.Support particles containing PEG ester groups are simply copolymerizedwith the other ingredients.

Glass-(silica-)based separation particles are also useful herein. Thesematerials typically contain an amine group that is reacted with ethyleneoxide or with an epichlorohydrin/PEG compound reaction product to formthen desired separation particles.

For example, four aminopropyl controlled pore glass products havingdifferent pore sizes are available from Sigma Chemical Co., St. Louis,Mo. These materials are said to have 150-250 μmoles at 200-400 mesh downto 40-100 μmoles at 80-120 mesh of primary amine per gram of material,with lessened activity/gram being present with increasing average poresize from 75 Å to 700 Å.

A preferred silica gel solid matrix can be prepared from the aminopropylsilica gel available from Sigma Chemical Co. that has about 1-2 mmolesof primary amine per gram of material. This material thus has about 5-to 10-times the loading capacity of the controlled pore glass product.This material has a size of about 200-425 mesh and an average pore sizeof about 150 Å.

Silica gel HPLC supports are also available from Sigma Chemical Co.having average pore diameters of about 60-80 Å and surface areas ofabout 420 to about 500 mm² /g. These particles are available in averageparticle diameters of about 5, 10, 30 and 60 microns. These silica-basedparticles can be converted into separation particles as discussed below.

Silica-based solid supports such as those discussed above are preparedfrom a suitable silica support such as silica gel or controlled poreglass by the reaction of an organosilicon compound with the support tocovalently link an aminoalkylene group to the silica. These reactionsare well known in the art. Amino-functional silanes having two or threeC₁ -C₃ alkoxy groups are particularly preferred organosilicon compoundsfor use in such linking reactions. Silanes having a mercapto functionalgroup and those having an acetoxy group convertible to a hydroxyl groupby aminolysis after covalent linking to the silicon-based matrix arealso available and can be used.

Preferred amino-functional silanes are ω-amino-C₂ -C₆ -alkylenetri-C₁-C₃ -alkoxy silanes. Exemplary compounds include4-aminobutyltriethoxysilane and 3-aminopropyltrimethoxysilane. Otherexemplary organosilanes from which a silica-based support particle canbe prepared include N-(2-aminoethyl)-3-aminopropylmethyldimethoxysilane,(aminoethylaminomethyl)phenethyltrimethoxysilane andN-(6-aminohexyl)aminopropyltrimethoxysilane. These materials areavailable from Huls America, Inc., Piscataway, N.J., and their synthesesand use are discussed in Silicon Compounds: Register and Review, 5thed., Anderson et al., eds., Huls America, Inc., Piscataway, N.J. (1991)and in the citations therein.

A glycidylsilane such as 3-glycidoxypropyltrimethoxysilane,(3-glycidoxypropyl)diethoxysilane or the like can also be reacted with asilica-based solid support followed by reaction with a desired PEGcompound such as PEG-2000 methyl ether to form desired separationparticles. Hydroxyl- and mercapto-functional alkoxysilanes such asbis(2-hydroxyethyl)-3-aminopropyltriethoxysilane and3-mercaptopropylmethyldimethoxysilane can also be reacted with asilica-based solid support followed by chain extension with ethyleneoxide to provide useful separation particles.

Cross-linked dextran- and agarose-based particles are well known in theseparation arts and are commercially available from Sigma Chemical Co.under trademarks Sephadex, Sephacryl, Sepharose and PDX.

Each of the above materials is based upon polymerized glucose moleculesthat can be polyethoxylated with ethylene oxide to provide desiredseparation particles. Alternatively, a desired PEG compound can be firstreacted with epichlorohydrin and the reaction product reacted with theglucose-based particles to form desired separation particles. Inaddition, cyanogen bromide activation can be used to add preformed PEGcompounds such as the before-discussed PEG methyl ethers. See, forexample Mathis et al., J. Chromatogr., 538:456-461 (1991) and thecitations therein.

Polyurethane/urea chemistry can also be utilized to prepare a desiredseparation particle. Here, a long chain PEG such as PEG-2000 or PEG-5000is reacted with a di-isocyanate alone, or admixed with a polyamine orpolyol to form a prepolymer. Exemplary di-isocyanates, polyamines andpolyols include methylenebis(4-phenylisocyanate), toluene di-isocyanate,diethylenetriamine, triethylenetetramine, triethanolamine,N,N,N'-tri(hydroxyethyl)ethylenediamine,N,N,N',N'-tetra(hydroxyethyl)ethylenediamine, and the like. Thatprepolymer is then reacted with C₂ -C₆ aliphatic diols or diamines toform polyurethanes and polyurea-urethanes, respectively. Exemplary diolsand diamines include ethylene glycol and ethylene diamine,1,4-butanediol and 1,4-butanediamine, as well as 1,6-hexanediol and1,6-hexanediamine. A C₁ -C₁₀ hydrocarbyl PEG 750-5000 ether as discussedherein can also be added at this stage as an end capping reagent as iswell known. Exemplary materials are discussed in Fong et al., Talanta,39:825(1992) and Jones et al., Anal. Chim. Acta, 182:61(1986).

A PEG compound, as is defined above by the formula X--(CH₂ CH₂ O)_(n)--CH₂ CH₂ R and discussed in detail hereinafter, is present on thesurface of the separation particles either intrinsically as a result ofthe copolymerization process that formed the particle or extrinsicallyfrom a grafting reaction carried out after the particle is formed.Although not wishing to be bound by theory, the data in hand tend toindicate that although the various solid support particles have pores,the separations contemplated here appear to operate from the outsidesurfaces of the particles and away from the pores. As a consequence,particles having smaller particle diameters, e.g. 200-400 mesh (75-38microns) and smaller (5-10 microns), are favored over particles havinglarger diameters, e.g. 80-120 mesh (180-115 micron), because of thegreater surface area per gram provided by the smaller particles. Inaddition, porous materials having smaller pore sizes are preferred.

The PEG compound present on the separation particles can itself be quitevaried in composition, but contains at least one poly(oxyethylene) chain[(--CH₂ CH₂ O--)_(n) ] having an average molecular weight of about 700to about 10,000, with a molecular weight of about 2,000 to about 5,000being more preferred. More specifically, the PEG compound group of theseparation particle corresponds to the formula --X--(CH₂ CH₂ O)_(n)--CH₂ CH₂ R where X, n and R are defined and discussed hereinbelow.

In the above formula, n is a number having an average value of about 15to about 225, and more preferably about 40 to about 130. It is wellknown that the higher molecular weight PEG compounds are usuallymixtures rather than pure compounds having a single molecular weight. Asa result, n, the number of ethyleneoxy repeating units, is a number thatis an average number.

The terminal R group is selected from the group consisting of --OH, C₁-C₁₀ hydrocarbyl ether having a molecular weight of up to aboutone-tenth of the --(CH₂ CH₂ O)_(n) -- portion, carboxylate, sulfonate,phosphonate and --NR¹ R² groups, where each of R¹ and R² isindependently hydrogen, C₁ -C₆ alkyl or C₂ -C₃ hydroxyalkyl or --NR¹ R²together form a 5- or 6-membered cyclic amine having zero or one oxygenatom or zero or one additional nitrogen atom in the ring.

Exemplary C₁ -C₁₀ hydrocarbyl ether groups are well known and includealkyl, alkenyl, alkynyl and aromatic ethers. Illustrative C₁ -C₁₀ ethersthus include methyl, which is most preferred, ethyl, isopropyl, n-butyl,cyclopentyl, octyl, decyl, 2-cyclohexenyl, 3-propenyl, phenyl,1-naphthyl, 2-naphthyl, benzyl, phenethyl and the like ethers. Theseether groups can also be named methoxy, ethoxy, isopropoxy, n-butoxy,cyclopentyloxy, octyloxy, decyloxy, 2-cyclohexenyloxy, 3-propenyloxy,phenoxy, 1-naphthoxy, 2-naphthoxy, enzyloxy and phenethyloxy. A C₁ -C₆hydrocarbyl group is a particularly preferred R group.

The molecular weight of a C₁ -C₁₀ hydrocarbyl ether can be up to aboutone-tenth of the weight of the --(CH₂ CH₂ O)_(n) -- portion of the PEGgroup. Thus, where n is 20, the --(CH₂ CH₂ O)_(n) -- portion has amolecular weight of 880 (20×44) so that the molecular weight of R can beup to about 90, or about the weight of a phenoxy group. It is morepreferred that the molecular weight of the C₁ -C₁₀ hydrocarbyl group beabout 0.2 to about 2 percent of the molecular weight of the --(CH₂ CH₂O)_(n) -- portion.

The R¹ and R² portion of an --NR¹ R² R group can individually andindependently be hydrogen, C₁ -C₆ alkyl or C₂ -C₃ hydroxyalkyl so that Rcan be a primary amine (--NH₂), a secondary amine (--NHR¹ or --NHR²) ora tertiary amine. The non-hydrogen R¹ and R² groups that are C₁ -C₆alkyl are as discussed before, e.g. methyl, ethyl, isopropyl, sec-butyl,cyclopentyl and hexyl, whereas a C₂ -C₃ hydroxyalkyl group is a2-hydroxyethyl, 2-hydroxypropyl or 3-hydroxypropyl group.

The nitrogen atom and the R¹ and R² portions of an --NR¹ R² group can,together with the depicted nitrogen atom, form a cyclic amine groupwhose ring contains 5- or 6-members. That 5- or 6-membered ring aminegroup can contain only carbon atoms in addition to the depictednitrogen, carbons plus one oxygen or carbons plus one nitrogen atom inaddition to that depicted in --NR¹ R². Exemplary cyclic amine groupsinclude piperidinyl, pyrrolidinyl, imidazolyl, piperazinyl andmorpholinyl groups.

In the above formula, X can be O, S, NH or N--(CH₂ CH₂ O)_(m) --R³. Useof an X group that is O, S or NH should be straightforward for theworker of ordinary skill. X is most preferably O, so that the separationparticles most preferably have a plurality of covalently bonded surface--O--(CH₂ CH₂ O)_(n) --CH₂ CH₂ R groups.

Where X is N--(CH₂ CH₂ O)_(m) --R³, two PEG groups can be present thatare the same or different. Thus, the --(CH₂ CH₂ O)_(n) --CH₂ CH₂ Rportion of the --X--(CH₂ CH₂ O)_(n) --CH₂ CH₂ R group is always present,and as such, a PEG compound containing about 15 to about 225 --(CH₂ CH₂O)-- repeating groups is always linked to the surface of a separationparticle. Where X is N--(CH₂ CH₂ O)_(m) --R³, m is zero and R³ ishydrogen, X reduces to --NH. However, m can also be about 15 to about225, and more preferably about 40 to about 130, as can n, as R³ can beCH₂ CH₂ R so that the nitrogen atom of an N--(CH₂ CH₂ O)_(m) --R³ groupcan be substituted by two identical PEG groups.

Where R is --OH, that terminal hydroxyl can be the result of the use ofpoly(ethylene glycol) itself or of an ethoxylation reaction withethylene oxide. A C₁ -C₁₀ hydrocarbyl ether R group can be preformed aswhere a PEG-methyl ether is used as is exemplified herein, or that ethergroup can be formed by an end-capping reaction of particles having ahydroxyl R group with a strong non-nucleophilic base such as sodiumhydride and a hydrocarbyl compound having a suitable leaving group suchas a halide (e.g. chloro or bromo) or a sulfate ester such as a trifate,mesylate or tosylate group.

Similar end-capping reactions can also be used to add the carboxylate,sulfonate, phosphonate and --NR¹ R² R groups. Exemplary compounds usefulhere include 2-chloroacetic acid, 4-(2-chloroethyl)piperidine and1-(2-chloroethyl)pyrrolidine. N-(2-chloroethyl)succinimide orphthalimide can be similarly added to a terminal R hydroxy groupfollowed by reaction with hydrazine to remove the phthalimide group andsubsequent reaction with a C₁ -C₆ alkyl group having a before-describedleaving group. Where only a single C₁ -C₆ alkyl group is desired, thefree primary amine provided after reaction with hydrazine can be blockedwith a removable blocking group such as t-butoxycarboryl (BOC) groupprior to alkylation followed by removal of the BOC group to provide adesired secondary amine. A desired R³ group can be similarly prepared.

It is also to be noted that although it is generally easier to preparedesired separation particles from a single PEG compound, even thoughthat compound may itself be a mixture, one can also prepare usefulseparation particles using PEG compounds of quite different chainlengths. The values of n for separation particles containing PEGcompounds of very different chain lengths nonetheless are about 15 to225.

For example, separation particles referred to herein as 107-5750 wereprepared by first reacting Merrifield's peptide resin particles withPEG-5000 methyl ether to form 107-5000 separation particles. Thoseseparation particles were then reacted with PEG-750 methyl ether to form107-5750 separation particles. The 107-5000 separation particlesexhibited a higher D_(w) value for TcO₄ ⁻¹ ions than did the 107-5750separation particles.

The amount of a PEG compound present on the surface of a separationparticle is provided by the percent CH₂ O/mm² of particle surface areavalue. That value is typically greater than about 8,000 and less thanabout 1,000,000, and is preferably greater than about 9,000 and lessthan about 20,000, particularly for the particularly preferredseparation particles prepared from 200-400 mesh Merrifield's peptideresin particles. Larger values are provided where still smallerparticles such as the 5 micron average diameter silica gel particles areused.

The percent CH₂ O/mm² of particle surface area (CH₂ O/mm²) value is,readily calculated using ¹³ C NMR integrals and the average particlesurface area in mm². ¹³ C Resonances for carbon atoms adjacent to anetherial oxygen differ from those for carbon atoms adjacent to othercarbons or other elements.

Thus, using the particularly preferred Merrifield's peptide resin-basedseparation particles as illustrative, one can determine the solid ¹³ CNMR spectrum and determine a ratio of the number of CH₂ O carbons tothose provided by the initial resin. Multiplication of that ratio by 100percent and division by the average particle surface area provides theCH₂ O/mm² value. The exemplary CH₂ O/mm² values utilized hereinafter arebased upon the surface area of 400 mesh particles. Similar solid phase¹³ C NMR determinations can be carried out using separation particlesprepared using the other before-discussed particles.

As noted previously, the separation particles are hydrophilic; i.e.,wettable. Wettability of useful separation particles can bequantitatively approximated by calculation of a dry weight conversionfactor (WCF) value for the particles. This value is approximate becausefor those separation particles that are only slightly wettable, thecalculations involve small differences between large numbers, and evenslight separation particle losses during manipulations can have a majorimpact upon the calculated WCF value. Nonetheless, WCF values can beuseful in further defining useful separation particles.

The WCF value for the separation particles is calculated by dividing theweight of dried separation particles by the weight of those particlesafter suspension in a specified aqueous medium under specifiedconditions followed by recovery and air-drying of those particles. Theseprocedures are detailed hereinafter.

Useful separation particles typically exhibit WCF values of about 0.9 toabout 0.01, with the particularly preferred separation particlesexhibiting WCF values of about 0.1 to about 0.6. The particularlypreferred 107-2000 and 107-5000 separation particles discussedhereinafter exhibited WCF values of about 0.32 and 0.37, respectively,indicating about 68 and 63 percents hydration, respectively, afterair-drying. The useful, but less preferred 107-750 separation particlesexhibited a WCF value of 1, indicating little, if any, post-dryinghydration.

The capacity of the separation particles for TcO₄ ⁻¹ in mmoles/gram ofseparation particles has not been determined because of the highradiation danger in carrying out the studies needed to make thedetermination. Nevertheless, studies carried out using 107-5000separation particles along with non-radioactive ammonium perrhenate (NH₄ReO₄), that although less soluble, behaves similarly to ammoniumpertechnetate under the conditions of a process contemplated herein, inthe presence of 2.31 molal (NH₄)₂ SO₄ at 25° C. indicate that theseparation particles can separate and retain at least about 1 μmole/gramof NH₄ TcO₄. Thus, the distribution value, D_(w), for TcO₄ ⁻¹ ion in thepresence of 10⁻⁵ -10⁻³ M ReO₄ ⁻¹ ion was substantially unchanged.

The above-described separation particles are contacted with an aqueoussolution that contains at least three components: (i) TcO₄ ⁻¹ ions, (ii)MoO₄ ⁻² ions and (iii) a poly(ethylene glycol) liquid/liquid biphaseforming amount of a dissolved salt whose anion can include MoO₄ ⁻² ion

All technetium isotopes are radioactive, whereas only some molybdenumisotopes are radioactive. Thus, the word radioactive is usually not usedas a modifier for technetium, whereas it is used with molybdenum asappropriate to a given circumstance.

As noted previously, the precursor for the most preferred technetiumisotope, ^(99m) Tc, is ⁹⁹ Mo, which can be formed by neutron activationof ⁹⁸ Mo or as a fission product of ²³⁵ U. The half-life of ⁹⁹ Mo isabout 66 hours, so little ⁹⁹ Mo remains about twenty-eight days (about672 hours) after ⁹⁹ Mo is formed.

Of the two ⁹⁹ Mo sources, the fission product material typically can beobtained as a highly radioactive mixture that is difficult to work with,but can provide relatively large amounts of ^(99m) Tc. The molybdatefrom ²³⁵ U fission is all, radioactive ⁹⁹ MoO₄ ⁻². The neutron activatedsource typically has lower concentrations of both ⁹⁹ Mo and ^(99m) Tc insolution with a relatively large quantity of non-radioactive molybdenum,⁹⁸ Mo. This latter source of ⁹⁹ Mo and ^(99m) Tc has typically beenuneconomical to use because of the relatively low concentration ofradionuclides present and the relatively high concentration ofnon-radioactive MoO₄ ⁻² (⁹⁸ MoO₄ ⁻²) ions. The present separationprocess can use either source of ^(99m) Tc, and provides economicviability for recovery of ^(99m) Tc from ⁹⁹ Mo produced by neutronactivation irradiation of ⁹⁸ Mo.

The MoO₄ ⁻² and TcO₄ ⁻¹ anions are present in solution along withappropriate cations, although other than providing charge neutralizationand water solubility, the cation is of little importance. The presenceof a cation is therefore to be presumed whenever MoO₄ ⁻² ion or TcO₄ ⁻¹ion is recited. Exemplary cations include the ammonium ion or alkalimetal cations such as lithium, sodium or potassium ions. Most polyvalentcation molybdates are too insoluble for use, with magnesium molybdateexhibiting a low solubility of about 14 grams/100 mL of water at 25° C.Ammonium, sodium and potassium cations are most preferred. The cation ofthe recovered TcO₄ ⁻¹ ions is that of the stripping solution or otherlast salt-containing aqueous solution to contact the TcO₄ ⁻¹ ion-boundseparation particles simply as a result of concentration-dependentexchange and mass action.

The third component of the aqueous solution is a poly(ethylene glycol)liquid/liquid biphase-forming amount of a dissolved salt whose anion caninclude the MoO₄ ⁻² ion As noted previously, it is well known thatparticular dissolved salts at particular concentrations and temperaturescause aqueous solutions of relatively high molecular weightpoly(ethylene glycols) to form a liquid/liquid biphase; i.e., twodistinct immiscible layers within the composition, in which one layer isrelatively rich in PEG and the other is relatively rich in salt. Thisphenomenon is often referred to as salting out the PEG.

The liquid/liquid biphase formation is caused by the presence ofwater-soluble salts whose anion is principally responsible for thebiphasic system. In addition, molybdate salts of copper, zinc andiron(II), whose sulfate salts can otherwise be used to form aliquid/liquid biphase, are insoluble so those cations are not usedherein. Thus, the before-mentioned ammonium and alkali metal ions arethe cations of choice with a given anion so that MoO₄ ⁻² salts do notprecipitate. Precipitation with other cations can be minimized by use ofa high pH value as can be obtained using at least 2M NaOH.

Keeping the molecular weight and concentration of the PEG constant,aqueous liquid/liquid biphase formation is generally favored byincreasing salt concentration to the point of saturation, and increasingtemperature between 20° and 60° C. At a constant concentration of a saltand temperature, aqueous liquid/liquid biphase formation is favored byincreasing PEG molecular weight, although aqueous liquid/liquid biphaseformation is not observed with a PEG having a molecular weight of about750 and lower.

The presence of an aqueous liquid/liquid biphase can be observed usuallyby an interface that forms between the two immiscible layers and/or byturbidity of the composition on mixing. The formulation of an analogouslayering is presumed to occur in the aqueous environment surrounding theseparation particles, but physical evidence for the existence of suchformation has not been observed.

An indirect assay for the amount of an appropriate salt present in theaqueous solution is therefore used herein. That indirect assay is basedon the observations (i) that salt concentrations that form aqueouspoly(ethylene glycol) liquid/liquid biphases in solution are useful in apresent process, and (ii) PEG-750 that does not form such a biphase whenfree in solution in the presence of a biphase-forming amount of salt canbe used when present covalently linked to the surface of separationparticles as the sole PEG compound present in the presence of thatamount of salt.

Thus, an aqueous poly(ethylene glycol) liquid/liquid biphase-formingamount of a dissolved salt that is present in an aqueous solution usedto contact the separation particles is an amount of a salt that causes asolution of PEG-2000 to form a biphase at a PEG-2000 concentration ofabout 4 to about 50 weight percent and at a temperature of 25° C.Several such salts and their concentrations are provided inAnanthapadmanabhan et al., Langmuir, 3:24-31 (1987). In addition, onecan carry out a simple study by preparing a solution of 4 to about 50weight percent PEG-2000 containing a desired concentration of a salt anddetermine whether biphase formation occurs at 25° C.

Exemplary anions useful in providing an aqueous poly(ethylene glycol)liquid/liquid biphase form salts with ammonium or alkali metal cations,and are provided in Table 1 below.

                  TABLE 1                                                         ______________________________________                                        Anion               Anion                                                     ______________________________________                                        Hydroxide           Chromate                                                  Fluoride            Molybdate                                                 Carbonate           Tungstate                                                 Silicate            Orthovanadate                                             Sulfate             Thiocyanate                                               Phosphate           Thiosulfate                                               Dihydrogen phosphate                                                                              Fluorosilicate                                            Hydrogen phosphate  Orthosilicate                                             Formate             Hydroxyethane-                                            Succinate           1,1-diphosphonate*                                        Tartrate            Vinylidene-                                               Citrate             1,1-diphosphonate*                                        ______________________________________                                         *The 2, 3 and 4 anion forms; i.e., the protonated forms, are useful.     

It is noted that MoO₄ ⁻² is an anion that can be used to form an aqueouspoly(ethylene glycol) liquid/liquid biphase. That fact is particularlyfortuitous where it is desired to form ^(99m) TcO₄ ⁻¹ using neutronactivation irradiation of non-radioactive ⁹⁸ Mo because no other saltneed be present to effect separation and recovery of the ^(99m) TcO₄ ⁻¹-containing salt. Thus, one can irradiate enriched ⁹⁸ Mo as the metal ortrioxide with neutrons and then dissolve the irradiated material in baseto form an aqueous poly(ethylene glycol) liquid/liquid biphase-formingamount of a MoO₄ ⁻² salt and then carry out a process contemplated hereto separate and recover the pertechnetate decay product.

A further way to characterize an aqueous poly(ethylene glycol)liquid/liquid biphase-forming amount of a dissolved salt is that theconcentration is about 0.05 molar to saturation, and the calculatedGibbs free energy of hydration (ΔG_(hyd)) of the anion is less thanabout -300 kJ/mole. Exemplary calculated ΔG_(hyd) values can be found inMarcus, J. Chem. Soc., Faraday Trans., 37:2995 (1991).

Another measure of the salting-out character of a contemplated aqueouspoly(ethylene glycol) liquid/liquid biphase-forming salt is thebefore-discussed B_(i) -coefficient of the Jones-Dole equation forviscosity that is discussed in Y. Marcus, Ion Solvation, John Wiley &Sons, Ltd., New York, (1985) page 124, values for which are provided inTable 5.13 therein. Those materials with a positive sign for the B_(i)-coefficient are lyotropic and cause biphase formation at the aboveconcentrations, whereas those materials having a B_(i) -coefficient witha negative sign are retained on the separation particles.

Biphase-formation is thus believed to be a function of thewater-structure-making or lyotropic property of the salt used. See, P.Becher, Dictionary of Colloid and Surface Science, Marcel Dekker, Inc.,New York, (1990) pages 95-96; Voet, Chem. Rev., 20:169-179 (1937). Thegreater is the water-structure-making property, the more readily anaqueous poly(ethylene glycol) liquid/liquid biphase is formed. Thosematerials that exhibit water-structure-breaking or chaotropic propertiesare retained on the separation particles.

It is also to be noted that once an appropriate amount of an aqueouspoly(ethylene glycol) liquid/liquid biphase-forming soluble salt ispresent, other anions and cations can also be present, and mixtures ofdifferent biphase-forming salts can be used to provide a biphase-formingamount. Thus, non-biphase-forming anions such as nitrate and chloridecan be present in the aqueous solution, and mixtures of biphase-forminganions such as hydroxide and carbonate can be used as thebiphase-forming soluble salt.

The pH value of the above-discussed aqueous solution is between 0 and14. Thus, the non-biphase-forming chloride and nitrate anions, as wellas biphase-forming sulfate and phosphate anions can be present as theirrespective acids. At a pH value of 12, achievable by use of 0.01 molarhydroxide ion, the concentration of hydroxide ion if used alone is toolow to form a desired biphase, so other anions such as carbonate,phosphate or sulfate are also utilized to provide an appropriate saltconcentration.

Continuing with the process steps, the before-described separationparticles are contacted with the before-described aqueous solution. Thiscontacting is an admixing manipulation and can occur in any vessel.Thus, one can simply admix the separation particles and an aqueoussolution in a laboratory vessel such as a beaker or flask. Morepreferably, the contacting is carried out in a chromatography column,which for separation and recovery of quantities of ^(99m) TcO₄ ⁻¹ anionsuseful in medical diagnoses typically needs only to have a volume ofabout 0.5 to about 2 mL.

Chromatography columns are well known in the art and are generallycylindrical, have an inlet means for adding an eluting solvent at ornear one end, an outlet means for egress of that solvent at or near theother end, and a means for maintaining the separation particles betweenthe inlet means and outlet means. Such columns are made of a materialthat is inert to the materials that are therewithin; i.e., glass,plastic such as polypropylene, or stainless steel, and can be designedto operate in any position; i.e., vertically, horizontally, or in acoil. For most medical uses of the ^(99m) TcO₄ ⁻¹ anion, a polypropylene2 mL syringe case (the syringe without the plunger) or a chromatographiccolumn, as are well known, held vertically with its wide end up foreluting solvent addition and using gravity flow of that eluting solventand a Luer-lock attachment or other outlet means at the bottom is quitesufficient. The body of the syringe case can hold the separationparticles in place between the open top and bottom, but it is preferredto use a glass or polypropylene frit or a small amount of glass wool onthe inside of the case above and below the separation particles tomaintain the separation particles in place.

The admixing of separation particles and MoO₄ ⁻² /TcO₄ ⁻¹ions-containing aqueous salt solution can take place with the separationparticles being dry or wet with water or another aqueous solution priorto contact. It is preferred, however, that the separation particles behydrated in an aqueous solution of a poly(ethylene glycol) liquid/liquidbiphase-forming salt prior to that contacting (admixing). Morepreferably, that salt solution contains the same salt at about theconcentration to be used for carrying out the process.

Where the contacting step is carried out in a laboratory vessel, theseparation particles can be premixed with an appropriate aqueous saltsolution, typically with some agitation, for a time period sufficientfor dry separation particles to hydrate (swell). The separationparticles are then recovered as by decantation of the liquid or byfiltration, and are then admixed with the aqueous solution containingthe MoO₄ ⁻² and TcO₄ ⁻¹ ions. Where the separation particles are withina chromatography column, a few free column volumes (fcv) of anappropriate aqueous salt-containing solution are preferably passedthrough the column prior to the cantacting step. Regardless of thetechnique used, appropriate hydration typically requires only a fewminutes.

The contacting forms a solid/liquid phase admixture. The contact ismaintained for a time period sufficient for the TcO₄ ⁻¹ ions to bind tothe solid phase separation particles and form a liquid phase aqueoussolution that contains MoO₄ ⁻² ions and is substantially free of TcO₄ ⁻¹ions.

Rates of binding of TcO₄ ⁻¹ ions to separation particles have not beendetermined. However, binding is almost instantaneous or requires only afew minutes at most inasmuch as studies with chromatography columns haveindicated that TcO₄ ⁻¹ ions do not co-elute with MoO₄ ⁻² ions as thelatter ions emerge from the bottom of the columns during loading.

The liquid aqueous phase is substantially free of TcO₄ ⁻¹ ions because⁹⁹ MoO₄ ⁻² ions have a first order decay to TcO₄ ⁻¹ ions so that at agiven time, some TcO₄ ⁻¹ ions may be formed that are not or have notbound to the separation particles and can be present in the liquidaqueous phase. For example, in a chromatography situation, an aqueouseluate containing ⁹⁹ MoO₄ ⁻² ions will have increasing amounts of TcO₄⁻¹ because of the decay of ⁹⁹ MoO₄ ⁻² ions. Those amounts are, usually,vanishingly small if present at all at a time within a few minutes ofelution.

The solid phase of the TcO₄ ⁻¹ ion-bound separation particles areseparated from the MoO₄ ⁻² ion-containing liquid phase formed during themaintenance step. This separation is carried out while maintaining theTcO₄ ⁻¹ ion-bound separation particles in the presence of an aqueoussolution of a poly(ethylene glycol) liquid/liquid biphase-forming amountof a salt.

In a process utilizing a chromatographic column, the degree of thisseparation can be enhanced by washing the column with an aqueoussolution of the same poly(ethylene glycol) biphase-forming salt usedduring the separation step or washing with a solution of another suchsalt. This wash or rinse step is carried out so that impurities that mayremain in the interstitial volume of the column are removed prior tostripping of the TcO₄ ⁻¹ ions so that a higher purity product can beobtained. For example, where the column is loaded using an aqueoussolution of 5M NaOH as the biphase-forming salt solution, the column canbe washed with more of that salt or one can use an aqueous solutioncontaining 3M K₂ CO₃. Such a wash step is preferred, but is notrequired.

Where a laboratory or other vessel such as a flask or beaker is used forthe process, the aqueous liquid phase formed after the maintenance stepcan be decanted off or separated by filtration or the like. Thatphysical separation is preferably followed by one or more washes withaqueous salt solution as discussed above.

Regardless of the procedure used, a second solid/liquid phase admixtureis preferably formed. That second solid/liquid phase admixture containsTcO₄ ⁻¹ ion-bound separation particles (solid phase) that are in thepresence of an aqueous solution of a poly(ethylene glycol) liquid/liquidbiphase-forming amount of a dissolved salt that is free of MoO₄ ⁻² ions.

That second solid/liquid phase admixture can be used separately forsubsequent recovery of the TcO₄ ⁻¹ ions. Thus, the separation of MoO₄ ⁻²and TcO₄ ⁻¹ ions can take place at one location, with the separatedsecond solid/liquid phase admixture being shipped to a second locationfor use as in a medical diagnostic procedure. This second solid/liquidphase admixture is utilized at least for shipment within a closedcontainer such as a vial, test tube or the like that itself is typicallycontained in a container that prevents leakage of radiation. In onepreferred embodiment of this aspect of the invention, the secondsolid/liquid phase admixture is present within a chromatography columnas the first-named container.

The separated TcO₄ ⁻¹ ions are freed from their bound state bycontacting (admixing) the TcO₄ ⁻¹ ion-bound separation particles with asecond aqueous solution that does not contain a poly(ethylene glycol)liquid/liquid biphase-forming amount of a dissolved salt to free theTcO₄ ⁻¹ ions from the separation particles and form an aqueous solutioncontaining free TcO₄ ⁻¹ ions along with their corresponding cations.Thus, a third solid/liquid phase admixture is formed where solid phaseconstitutes the hydrated separation particles.

Distilled or deionized water is a convenient second aqueous solution forthis purpose. Also useful are sodium chloride solutions such as isotonic0.9N NaCl solutions. The second aqueous solution can containbiphase-forming salts such as potassium carbonate and potassiumphosphate, but the concentration of those salts is less than an aqueouspoly(ethylene glycol) liquid/liquid biphase-forming amount. This secondaqueous solution is sometimes referred to herein as a stripping solutionbecause of its use to strip the TcO₄ ⁻¹ ions from the separationparticles.

The pH value of a stripping solution can be from about zero to about 14,but is more preferably about 6 to 8.

The aqueous solution containing free TcO₄ ⁻¹ ions is then recovered.

In a chromatographic environment, one can simply wash the columncontaining the separation particle-bound TcO₄ ⁻¹ ions whose liquid phaseis free from MoO₄ ⁻² ions with the desired second aqueous solution, andthen collect the eluate. As is seen from FIGS. 12 and 13, elution of thepreviously bound TcO₄ ⁻¹ ions can be quite sharp. Where the separationis carried out in a laboratory or other vessel, one can simply wash(contact and mix) the appropriate separated solid phase with the secondaqueous solution and then collect the resulting liquid phase as byfiltration or decantation.

As noted earlier, the technetium isotope usually used in medicaldiagnostics is ^(99m) Tc that has a relatively short half-life of about6 hours. Additionally, ⁹⁹ Mo, from which ^(99m) Tc and ⁹⁹ Tc arise, alsohas a relatively short half-life of only about 66 hours. Thus, both^(99m) Tc and ⁹⁹ Mo have decayed to ⁹⁹ Tc within about twenty-eight daysof their manufacture.

On the other hand, ⁹⁹ Tc has a half-life of about 2×10⁵ years, and oncemade, remains a radiation hazard. This form of technetium, ⁹⁹ Tc, ispresent in a number of nuclear wastes from which it would be desirableto be separated.

These wastes, such as those at the Westinghouse Hanford facility,contain ⁹⁹ Tc as aqueous TcO₄ ⁻¹ salts and are typically free of MoO₄ ⁻²ions. In particular, these wastes contain a sufficient concentration ofbiphase-forming salts (typically NaOH) to permit separation and recoveryof ⁹⁹ TcO₄ ⁻¹ ions without pretreatment. The present invention alsoprovides a process for separating and recovering TcO₄ ⁻¹ ions from theseand other aqueous solutions, regardless of the presence of MoO₄ ⁻² ions.In accordance with this more general process:

(a) before-discussed separation particles are contacted with an aqueoussolution that contains (i) TcO₄ ⁻¹ ions and (ii) an aqueouspoly(ethylene glycol) liquid/liquid biphase-forming amount of adissolved salt, as also discussed before, to form a solid/liquid phaseadmixture;

(b) that solid/liquid phase admixture is maintained for a time periodsufficient to form TcO₄ ⁻¹ ion-bound separation particles and an aqueoussolution that is substantially free of TcO₄ ⁻¹ ions, as is alsodiscussed before;

(c) the TcO₄ ⁻¹ ion-bound separation particles are preferably separatedfrom the aqueous solution of step (b) in the presence of an aqueoussolution of a poly(ethylene glycol) liquid/liquid biphase-forming amountof a salt to form a second solid/liquid phase admixture containing TcO₄⁻¹ ion-bound separation particles;

(d) the TcO₄ ⁻¹ ion-bound separation particles of that secondsolid/liquid admixture are contacted with a second aqueous solution thatdoes not contain a poly(ethylene glycol) liquid/liquid biphase-formingamount of a dissolved salt to free the TcO₄ ⁻¹ ions and form an aqueoussolution containing free TcO₄ ⁻¹ ions; and,

(e) the free TcO₄ ⁻¹ ion-containing aqueous solution is recovered.

It is thus seen that the first-disclosed process is a specificembodiment of the above-recited process. The preferences noted for thatfirst disclosed process are maintained for the above-recited process.

A before-described process is typically carried out at ambient roomtemperature. However, such a process can also be carried out at anytemperature above the freezing point and below the boiling point of theaqueous solutions utilized. A contemplated process is typically carriedout at ambient atmospheric pressure, but can also be carried out at anelevated pressure.

Results

Reaction of the sodium alkoxide of poly(ethylene glycol 2000 methylether) (Me-PEG-2000) with a chloromethylated polystyrene (with 1 percentdivinylbenzene cross-linking; Aldrich Chemical Co.) also referred to asMerrifield's peptide resin afforded a dirty white material. The reactedMerrifield's peptide resin [cross-linked poly(styrene-co-vinyl benzylchloride)] was no longer a free flowing solid like the precursor beads,however, the new material maintained a resin-like consistency. Whencontacted with water the material was evenly dispersed and readilyhydrated. Gravimetric analysis revealed a dry weight conversion factorof 0.316 (or 68.4 percent water) for the Me-PEG-2000 modified material,indicating extensive wettability and a high potential for aqueousbiphasic behavior. Uptake studies for pertechnetate from a variety ofbiphase-forming salt solutions showed high weight distribution ratiosand will be discussed below.

Four other polystyrene-based chromatographic materials were preparedwith the monomethyl ether derivatives of PEG-350, PEG-750, PEG-5000, andPEG-5000+PEG-750, with most of the work being done with monomethylethers of PEG-350, -750, -2000 and -5000. These materials weresynthesized to investigate the influenc of PEG molecular weight on metalion partitioning and aqueous biphasic behavior. These resins wereprepared in a manner identical to that for Me-PEG-2000, and all affordeddirty white bead-like solids. Separation particles prepared usingMe-PEGs having molecular weights of 350, 750, 2000, 5000 and both 5000and 750 are named 107-350, 107-750, 107-2000, 107-5000 and 107-5750respectively.

A number of metal cations including Na⁺, Cs⁺, Ca⁺², Sr⁺², Mn⁺², Co⁺²,Cd⁺² and Tl⁺¹ were assayed for retention by 107-2000 from both water and5.05 molal (m) (NH₄)₂ SO₄. None of the above metal cations was retainedby the material, and this is in keeping with their behavior inliquid/liquid aqueous biphasic separations where none of those metalspartitions to the PEG-rich phase. Because the pertechnetate anionspartition to the PEG-rich phase in liquid/liquid aqueous biphasicsystems without the aid of an extractant, [Rogers et al., Solvent Extr.Ion Exch., (in press 1995); Rogers et al., In Aqueous BiphasicSeparation: Biomolecules to Metal Ions; Rogers and Eiteman, eds; Plenum:New York, 1995; in press; Rogers et al., Solvent Extr. Ion Exch., 1994,(in press 1995); Rogers et al., Sep. Sci. Technol., 28:1091 (1993)] thation was used as a probe for biphasic character.

Weight distribution ratios for TcO₄ ⁻¹ compounds have been determinedfrom (NH₄)₂ SO₄, K₂ CO₃, K₃ PO₄, and NaOH solutions as exemplary. Thesesalts are known as liquid/liquid biphase forming anions and cover abroad range Of chemical characteristics.

Weight distribution ratios for TcO₄ ⁻¹ anions onto unmodifiedchloromethylated polystyrene-1-percent-divinylbenzene from both waterand 5.05 m (NH₄)₂ SO₄ were near unity. Pertechnetate retention by107-2000 from water was extremely low affording a D_(w) of only 8.7.

The amount of solute on the separation particles is determined by adifference method and therefore D_(w) values less than one are difficultto obtain due to error inherent in the assay method. D_(w) values lessthan 20 generally indicate little if any retention. A D_(w) value ofabout 200 is maximally observed in a liquid/liquid extraction of TcO₄ ⁻¹ions in NaOH using 20-70 weight percent aqueous PEG-2000.

FIG. 1 shows D_(w) 's for TcO₄ ⁻¹ anions with 107-350 at 25° C. usingthe before-mentioned four liquid/liquid biphase forming salts. All ofthe weight distribution ratios were below ten and indicated no retentionof pertechnetate by these potential separation particles. The dry weightconversion factor for this material is 1.0, meaning that it is nothydrated within the limits of this measurement. In fact, this materialbehaves very similarly to the unmodified chloromethylatedpolystyrene-1-percent-divinylbenzene. Both materials had extremely lowwettabilities, are not evenly dispersed in water, and consequently showno aqueous biphasic partitioning behavior.

Separation particles 107-750 showed an appreciable increase in TcO₄ ⁻¹anions distribution with a maximum D_(w) of 460 at 4.08 m (NH₄)₂ SO₄(FIG. 2). Pertechnetate retention started low, maximized, and thentailed from PO₄ ⁻³, CO₃ ⁻², and SO₄ ⁻² solutions. Sodium hydroxideafforded the lowest weight distribution ratios that sharply decreasedfrom a maximum D_(w) of 96 at 2.78 m NaOH.

Separation particles 107-750, like 107-350, had a dry Weight conversionfactor of 1.0. Although not as hydrophobic as 107-350, this materialdispersed evenly in water and is useful, but difficult to handle becauseit has a gummy consistency.

Separation particles 107-2000 were the first material to show a behaviorsimilar to aqueous biphasic partitioning. The potential of this materialwas suggested by its dry weight conversion factor which indicated a 68.4percent water content. From high ionic strength solutions, weightdistribution ratios were quite high as depicted in FIG. 3. The highestD_(w) values were 4500, 6200, 1900, and 880 from 5.05 m (NH₄)₂ SO₄, 5.92m K₂ CO₃, 3.14 m K₃ PO₄, and 4.41 m NaOH, respectively. D_(w) 's fromsodium hydroxide peaked at an intermediate salt concentration (4.41 m)and then began to decrease. The remaining salts all showed a reasonableincrease in weight distribution ratios, with K₂ CO₃ affording thehighest D_(w) values.

FIG. 4 depicts D_(w) for TcO₄ ⁻¹ anions using 107-5000. These weightdistribution ratio profiles have the same general features as observedfor 107-2000, except that there is an increase in D_(w) for TcO₄ ⁻¹anions from NaOH rather than the intermediate maxima observed for107-2000. This behavior is not well understood. The maximum weightdistribution ratios are 7000, 19000, 5200 and 2500 from 5.05 m (NH₄)₂SO₄, 5.92 m K₂ CO₃, 3.14 m K₃ PO₄, and 8.33 m NaOH, respectively. Thesevalues are about two to three times those obtained with 107-2000, withthe maximum D_(w) values from the K₂ CO₃ solution as observed for107-2000. Interestingly, the dry weight conversion factor of 0.374 for107-5000 was higher than that for 107-2000, indicating a lower watercontent.

FIG. 5 shows D_(w) for TcO₄ ⁻¹ anions vs. molality of (NH₄)₂ SO₄ for thefour different molecular weight resins. Weight distribution ratios for107-350 are extremely low, whereas 107-750 was two orders of magnitudehigher, but still showed a relatively flat slope. Separation particles107-2000 and 107-5000 D_(w) values increased steadily as the molality of(NH₄)₂ SO₄ increased, reaching 7000 for 107-5000 at 5.05 m.

FIG. 6 D_(w) for TcO₄ ⁻¹ anion vs molality of K₂ CO₃, showed thebroadest range in weight distribution ratios for the four aqueousbiphasic resins. The span covered four orders of magnitude from the lowaround unity for 107-350 to the maximum of 19000 at 5.92 m K₂ CO₃ for107-5000. The profiles for 107-350 and 107-750 in K₂ CO₃ resembled thosefrom (NH₄)₂ SO₄, although the D_(w) values for 107-750 were somewhatlower in this basic media. Contrasting this behavior are 107-2000 and107-5000 that have weight distribution ratios for pertechnetate in CO₃⁻² solutions about twice those from the ammonium sulfate systems. D_(w)values for the two highest molecular weight PEG 107 materials alsoclimbed more rapidly in K₂ CO₃ than in (NH₄)₂ SO₄, however a leveling ofthe slopes above 4.82 m K₂ CO₃ was noted.

K₃ PO₄ solutions afforded weight distribution ratio profiles thatmimicked (NH₄)₂ SO₄, but at significantly lower concentrations of salt.FIG. 7 depicts the efficiency of the four 107 resins for TcO₄ ⁻¹ anionretention from K₃ PO₄ solutions.

Once again, 107-350 and 107-750 had low weight distribution ratios andessentially flat profiles. D_(w) values with 107-2000 and 107-5000climbed steadily to their respective maxima of 1900 and 5200 at 3.14 mK₃ PO₄. As with (NH₄)₂ SO₄, no leveling of the D_(w) profiles occurredin K₃ PO₄. Around 3 m salt the weight distribution ratios are comparablefor 107-2000 (3.14 m K₃ PO₄, D_(w) =1900; 3.24 m (NH₄)₂ SO₄, D_(w)=1500).

Sodium hydroxide afforded the lowest D_(w) values of all the saltsystems studied. FIG. 8 plots D_(w) for TcO₄ ⁻¹ anion vs. molality ofNaOH and shows some unique behavior. 107-750 D_(w) values started around100, as they did for the other three salts, however a steady decreasedown to D_(w) =1 occurred in NaOH. A tailing and leveling, respectively,were observed for 107-2000 and 107-5000 above 6.25 m NaOH. This behavioris not yet understood, but the basic K₂ CO₃ solutions showed a similarleveling effect that was not observed in the weakly acidic (NH₄)₂ SO₄solutions.

The four phase-forming salts utilized in these studies encompass a broadrange of chemical characteristics. The pH value range varies from around4-5 for (NH₄)₂ SO₄ to 14 for NaOH, and from chemically inactive (SO₄ ⁻²,CO₃ ⁻², PO₄ ⁻³) to extremely caustic (OH⁻). These salts also represent aseries of mono-, di-, and trianionic aqueous liquid/liquidbiphase-forming anions that cover a broad concentration range.

Pertechnetate distribution was exceedingly low for 107-350.Consequently, the following discussion about the partitioning behaviorin the above four salt solutions is limited to 107-750, 2000, and 5000separation particles.

FIGS. 2-4 illustrate the relative orderings of weight distributionratios as a function of salt concentration. In each case, K₃ PO₄ wascapable of binding (salting out) the pertechnetate anion to theseparation particles at the lowest salt concentration, and at highermolalities (NH₄)₂ SO₄ and K₂ CO₃ afforded the highest weightdistribution ratios. In the approximate range 1.8-3.1 m K₂ CO₃, (NH₄)₂SO₄, or K₃ PO₄, pertechnetate distribution is roughly equivalent on eachmodified resin. The monovalent hydroxide anion is the least efficientmedium for pertechnetate extraction, nonetheless a maximum weightdistribution ratio of 2500 was obtained using 107-5000 separationparticles.

FIGS. 5-8 show one of the most important variables affectingpertechnetate distribution; i.e., the molecular weight of the polyether.Particles 107-350 performed poorly in each of the four salt solutions,whereas separation particles 107-750 were in the middle and 107-2000 and107-5000 (average n=about 44 and 113, respectively) performed muchbetter and quite similarly. The molecular weight of the polymer had anobvious affect on solute distribution in these solid/liquid separations,and this is in keeping with results from liquid/liquid separations.[Rogers et al., Solvent Extr. Ion Exch., (in press 1995); Rogers et al.,in Aqueous Biphasic Separation: Biomolecules to Metal Ions, Rogers andEiteman, eds., Plenum, New York. (1995) in press; Walter et al., AqueousTwo-Phase Systems, in Methods in Enzymology, Academic Press, San Diego,Vol. 228 (1994); Albertsson, Partition of Cell Particles andMacromolecules, 3rd ed., John Wiley & Sons, New York (1986);Partitioning in Aqueous Two-Phase Systems, Theory, Methods, Uses andApplications in Biotechnology, Walter et al., eds., Academic Press,Orlando (1991)]

In order for an aqueous biphase to form in the liquid/liquid mode, themolecular weight of the PEG must be high enough so that it can be saltedout by a sufficient concentration of biphase-forming salt. Thisobservation suggests a dependence on the molecular weight of the Me-PEGpolymer used illustratively here, but does not predict the weightdistribution ratios in excess of 100 for 107-750 separation particles,(PEG's of this molecular weight do not form heterogeneous two-phasesystems in the liquid/liquid mode at ambient temperature), nor does itexplain the similar behavior of 107-2600 and 107-5000 separationparticles.

One explanation for the poor performance of the low molecular weight 107materials can. be found in their low wettabilities. Neither 107-350particles nor 107-750 separation particles were hydrated withinmeasurability after contact with water, whereas 107-2000 and 107-5000separation particles were only 31.6 and 37.4 percent solid afterhydration.

It is thus believed that if the Me-PEG is not suitably hydrophilic, isnot capable of making the support suitably hydrophilic, and is also notof sufficient molecular weight to participate in a genuine aqueousbiphasic interaction, its partitioning characteristics will be poor.

The unpredictably small difference in the TcO₄ ⁻¹ anion retentionproperties of 107-2000 and 107-5000 separation particles is notcompletely understood. One possible explanation centers on the amount ofMe-PEG present on the support, and its location on the surface or withinthe pores of the material. The support material is a microporouspolystyrene-1-percent-divinylbenzene copolymer with a mesh range of200-400 (about 75-38 microns). Diffusion and grafting of Me-PEG into thepores is inevitable. However, the extent of grafting in the pores shoulddecrease as the polymer molecular weight increases. Some electronmicroscopy and ¹³ C relaxation studies have been done on polystyrenebound ethylene oxide polymers [Poly(Ethylene Glycol) Chemistry:Biotechnical and Biomedical Applications, Harris, ed., Plenum Press, NewYork (1992)]; and this work suggests a dual activity at the surface andin the pores.

Solid state NMR data on the four 107 materials and on the unmodifiedchloromethylated polystyrene-1-percent-divinylbenzene precursor showed asteady decrease in the ethylene oxide concentration for separationparticles 107-750 through 107-5000. This finding is in keeping with thesuggested decrease in grafting yields as the molecular weight of the PEGincreases, [Poly(Ethylene Glycol) Chemistry: Biotechnical and BiomedicalApplications, Harris, ed., Plenum Press, New York 1992] which is largelydue to steric hindrance.

The finding that there is a higher concentration of Me-PEG on separationparticles 107-2000 than 107-5000 lends some insight into the smalldifference in the partitioning behavior of these two chromatographicmaterials. Whereas the partitioning of metal ions in aqueous biphasicsystems is enhanced by increasing PEG molecular weight, [Rogers et al.,Solvent Extr. Ion Exch., (in press 1995)] this trend may not rigorouslyhold in these solid-supported separations due to the steric hindranceimposed by the larger polymers that can lead to a decrease in surface(and pore) grafting yields. [Poly(Ethylene Glycol) Chemistry:Biotechnical and Biomedical Applications, Harris, ed., Plenum Press, NewYork 1992]

The higher Me-PEG concentration on 107-2000 separation particles is alsoin keeping with the dry weight conversion factor data. The higherpolymer concentration on 107-2000 separation particles affords aslightly lower percent solid of 31.6 percent, opposed to the 37.4.percent solid for 107-5000 separation particles.

From these observations, Me-PEG-2000 is one particularly preferredchoice for the grafting approach. Separations with 107-2000 separationparticles are efficient in the aqueous liquid/liquid biphase-formingsalts (as opposed to the low retention properties of 107-750 separationparticles) and have reasonably high concentrations of Me-PEG-2000 on theresin. On the other hand, 107-5000 separation particles provided higherD_(w) values, making Me-PEG-5000 separation particles anotherparticularly preferred choice for the grafting approach.

Distributions of pertechnetate in PEG-2000-based liquid/liquid systemsand D_(w) values in 107-2000 separation particle systems are depicted inFIG. 9. Uptake of TcO₄ ⁻¹ ions by 107-2000 separation particles wasabout an order of magnitude larger than extraction by the PEG-rich phaseof the liquid/liquid system. The reasons for this are not yet clear, butcould be related to the preorganization of the polymers induced by theircovalent bonding to the support material or to the higher concentrationof Me-PEG on the resin due to the elimination of PEG loss due to itssolubility in the salt-rich phase.

The performance of 107-2000 involving separations from real-world wastematrices has been excellent. The separation of the pertechnetate anionfrom high level defense wastes is currently of great concern [Kupfer,"Preparation of Nonradioactive Substitutes for Radioactive Wastes",Rockwell Hanford Operations (1981); Schulz, et al., "Candidate Reagentsand Procedures for the Dissolution of Hanford Site Single-Shell TankSludges":, Westinghouse Hanford Co., (1991); Kupfer, "Disposal ofHanford Site Tank Waste", Westinghouse Hanford Co., (1993)] due to thelong half-life of ⁹⁹ Tc (2.12×10⁵ years) and its environmental mobilityas the pertechnetate anion. The compositions of three representativesimulated Hanford waste streams, Hanford tank SY-101 (SY-101),neutralized current acid waste (NCAW), and single shell tank waste(SST), showed sufficient concentrations of phase forming anions (namelyOH⁻) to support aqueous biphasic separations. [Rogers et al., SolventExtr. In Exch., (in press 1995)] Preliminary studies of TcO₄ ⁻¹ anionretention by 107 materials from these three waste stimulants showed thatTcO₄ ⁻¹ anions could be efficiently separated from these very complexmatrices.

FIG. 10 shows the performance of the four different 107 materials inthree different simulated Hanford tank wastes. Pertechnetate extractionby the lightest PEG 107 material (107-350) was poor, whereas 107-750separation particles reached a maximum D_(w) of 54 in the SST wastesimulant. Separation particles 107-2000 performed slightly better than107-5000, although the weight distribution ratios are very similar. Thehighest D_(w) of 410 was obtained for 107-2000 separation particles inthe SY-101 simulant and illustrates the use of these materials inreal-world separations. An important point here is that no pH adjustmentof these highly basic waste simulants was carried out. Few extractionschemes exist for carrying out separations in such alkaline conditionsand this is an important achievement of the 107 material approach.

The low weight distribution ratios obtained for pertechnetate from waterwith 107-2000 indicate a solution to the stripping difficulties plaguingthe liquid/liquid method. Without a sufficiently high concentration ofaqueous liquid/liquid biphase-forming anions, no retention ofpertechnetate was observed. In a column mode, the TcO₄ ⁻¹ ions can beextracted from mobile phases of aqueous liqUid/liquid biphase-forminganions, bound to the solid support of separation particles, and thenstripped using water or an aqueous solution that does not contain apoly(ethylene glycol) liquid/liquid biphase-forming amount of salt.

The solid-supported aqueous biphasic-type separations have been shown tobe an effective alternative to the liquid/liquid approach. Many of thedisadvantages of the latter have been addressed, namely that loss of thephase-forming polymer to the salt-rich phase has been eliminated bytethering the polymer to an inert support, and perhaps most importantlyis the ability to strip partitioned solutes using water or an aqueoussolution of a salt that does not form an aqueous liquid/liquid biphasewith PEG. Several advantages have also come forth including theobservation that less salt is required to effect a separation, and thatseparations at a given concentration of salt (and comparable molecularweight polyethers) can be an order of magnitude or more higher on the107 material than in a liquid/liquid biphase separation. In addition,the covalent linkage to the cross-linked polystyrene particle affordsgood chemical stability over a wide pH value range.

Materials and Methods

Tetraethylene glycol, Me-PEG-350,Me-PEG-750, PEG-2000, Me-PEG-2000,Me-PEG-5000, poly(methylmethacrylate), and chloromethylatedpolystyrene-1-percent-divinylbenzene beads (Merrifield's peptide resin;200-400 mesh) were obtained from Aldrich. All were used without furtherpurification. Reagent-grade (NH₄)₂ SO₄, K₂ CO₃, K₃ PO₄, and NaOH wereused as received. The reagents and procedures for preparing the Hanfordsimulated waste solutions have been reported. [Rogers et al., SolventExtr. Ion Exch., (in press 1995)] A water solution of NH₄ ⁹⁹ TcO₄ wasobtained from Isotope Products Laboratories. Tetrahydrofuran (THF) wasof reagent quality, was distilled from the sodium benzophenone ketylradical, and was transferred and stored under argon prior to use. Allwater was deionized using commercial deionization systems.

Metal Ion Uptake Studies

All separation particles were stored in tightly capped containers andwere not exposed to air for any extensive period of time so as to avoida change in water content. All weight distribution ratios wereradiometrically determined by batch contacts of the resin with thedesired analyte-containing solution. The dry weight distribution ratiois defined as: ##EQU1## where A_(o) =the activity of the solution priorto contact with the resin, A_(f) =the activity of the solution aftercontact with resin, V=volume (mL) of solution contacted with resin,m_(R) =mass (g) of resin, and wcf=the dry weight conversion factorrelating the mass of the hydrated resin to its dry weight.

The D_(w) studies were carried out in the following manner. Theradiotracer was added to 1.2 mL of the solution of interest, gentlymixed, and a 100 μL aliquot was removed for radiometric counting todetermine the initial activity of the solution (A_(o)). One mL of theremaining solution (V) was added to a known mass of hydrated resin(m_(R)) and centrifuged for one minute. The solution was then stirredgently (so that the resin was just suspended in the solution) for 30minutes, followed by one minute of centrifugation, and another 30minutes of stirring. After one additional minute of centrifugation, thesolution was pipeted away from the resin and filtered through a 45 μmpipet-tip filter so that any suspended resin would be removed. A 100 μLaliquot was then removed for counting the final activity of the solution(A_(f)).

Synthesis of Chromatographic Materials Williamson Ether Syntheses of 107Materials

The syntheses of 107-350 particles and 107-750, 107-2000, and 107-5000separation particles were all carried out in a similar manner and anyunique aspects of the individual syntheses will be noted.

Thus, under an Ar atmosphere NaH (0.38 g, 16 mmol) was passed into a 1 L3-neck flask that was capped and brought out to the bench top. Under apositive flow of Ar the system was equipped with a 400 mL slow additionfunnel and a water jacketed reflux condenser. THF (≈400 mL) was thentransferred to the addition funnel via standard cannula techniques. Aportion of the THF (100 mL) was drained into the round-bottom flask inorder to suspend the NaH with stirring.

Either Me-PEG-350 (959 μL, 3.0 mmol), Me-PEG-750 (2.25 g, 3.0 mmol), orMe-PEG-5000 (15.0 g, 3.0 mmol) was then added to the addition funnelunder a positive Ar flow. The same procedure was utilized in thepreparation of 107-2000 separation particles, except that a 3:1 molarexcess of Me-PEG-2000 alkoxide to resin active sites was prepared withNaH (1.07 g, 45 mmol) and Me-PEG-2000 (18.0 g, 9.0 mmol). TheMe-PEG-750, Me-PEG-2000, and Me-PEG-5000 are solids that were meltedinto the THF in the addition funnel with the aid of a hot air gun. Thissolution was then added dropwise over approximately one-half to one hourto the NaH suspension at zero degrees C. Once the addition was complete,the solution was stirred at zero degrees C. for one hour.

The mixture was then warmed to room temperature with stirring, followedby the addition of chloromethylated polystyrene-1-percent-divinylbenzene(3.0 g, 3.0 mmol reactive sites) under a positive Ar flow. The reactionwas stirred at 25° C. for one to two hours followed by 36 to 72 hours ofrefluxing with stirring. The resulting murky solutions were thenfiltered using a large Buchner funnel, and the resulting solids wereexhaustively extracted with THF in a Soxhlet extraction apparatus for 72hours to remove unbound Me-PEG. The extracted resins were then dried invacuo and small aliquots were hydrated for the weight distribution ratiostudies as needed. Combustion analyses of the precursor chloromethylatedpolystyrene-1-percent-divinylbenzene and the dry 107 materials showed adecrease in carbon percentage consistent with the grafting of Me-PEGmoieties. Because the Me-PEG molecular weights are average values andthe functionalization of the resin is reported as an approximate value,no compositional information other than the observed decrease in carbonpercentages can be obtained. Analysis found for chloromethylatedpolystyrene-1-percent-divinylbenzene: (percent) C, 88.44; H, 7.35. Foundfor 107-350: C, 66.65; H, 6.64. Found for 107-750: C, 68.68; H, 7.75.Found for 107-2000: C, 67.06; H, 8.62. Found for 107-5000: C, 67.78; H,8.16.

Procedure for the ^(99m) TcO₄ ⁻¹ /⁹⁹ MoO₄ ⁻² Separation Using 107-5000as Solid Support

A disposable plastic column equipped with a Luer-lock stopcock andporous plastic bed support was slurry packed with 107-5000 separationparticles in water and backwashed. A porous plastic frit was placed ontop of the bed to prevent its disruption during the addition of eluent.The bed volume was 1.63 mL and the free column volume (fcv) wasdetermined by ⁹⁹ MoO₄ ⁻² breakthrough. The fcv of 0.392 mL wascomparable to that obtained using a sodium breakthrough/flame test. Alleluate volumes were calculated gravimetrically using the respectivesolution densities.

The 107-5000 separation particle-containing column was equilibrated with5.00 mL (12.8 fcv) of 5.0M NaOH. Thereafter, 11.2 mL (28.6 fcv) of Na₂⁹⁹ MoO₄ in 5.0M NaOH was eluted on the column using gravity flow (<0.3mL/minute). Prior to rinsing, the reservoir was washed three times with3 mL of K₂ CO₃ to remove residual Na₂ ⁹⁹ MoO₄. The column was rinsed ofNa₂ ⁹⁹ MoO₄ by elution with 4.3 mL (11.0 fcv) of 3.0M K₂ CO₃.

Water [13.3 mL (33.0 fcv)] was passed into the column and over the resinto remove the Na^(99m) TcO₄. Activity was observed in the eluate afterseveral fcv indicating that ^(99m) TcO₄ ⁻¹ anion was being removed. Thewater strip was accompanied by a 30 percent swelling of the resin.

The total γ activity of ⁹⁹ MoO₄ ⁻² ions eluted on the column was5.19×10⁶ cpm. The sum of the activity of ^(99m) TcO₄ ⁻¹ anions strippedfrom the column was 1.97×10⁷ cpm. (The ^(99m) Tc activity is higher thanthe ⁹⁹ Mo due to the higher conversion to γ for the ^(99m) Tc nuclide.)From 49-54 fcv, 1.79×10⁷ cpm of ^(99m) TcO₄ ⁻¹ were collected, whichcorresponds to 91 percent of the ^(99m) Tc activity being recovered infive fcv (1.96 mL).

An exemplary plot of the elution of ⁹⁹ MoO₄ ⁻² and ^(99m) TcO₄ ⁻¹ anionsfrom this column is shown in FIG. 11. Smaller samples of eluate weretaken at the beginning and end of peaks on the chromatogram, whereaslarger cuts were sampled during plateaus. As a result, the ordinate ofthe chromatogram has units of cpm/mL so that all activities are on auniform scale.

FIG. 12 shows the same elution curves on a broken axis scale. Followingbreakthrough, the ⁹⁹ MoO₄ ⁻² anions eluted steadily forming a plateauduring the load phase. The K₂ CO₃ rinse showed a steady drop in ⁹⁹ MoO₄⁻² anion activity and reached background after seven fcv. The waterstrip showed ^(99m) TcO₄ ⁻¹ anions coming off after eight fcv, and thispeak showed some tailing and split peaks that are as yet unexplained.

Insoluble Copolymer Beads Preparation A

Insoluble, cross-linked copolymer beads (100 g) were prepared bysuspension polymerization of 67.47 weight percent vinylbenzyl chloride,23.03 weight percent styrene, 5.0 weight percent divinylbenzene, and 0.5weight percent benzoyl peroxide; ethylstyrenes were also present fromthe technical grade divinylbenzene. To introduce porosity, an equalamount of 1:1 (w/w) mixture of toluene and dodecane was added. Theentire polymerization mixture was placed in a cylindrical reactorequipped with overhead stirrer, reflux condenser and thermometer, andwas heated at 60° C. for one hour, 70° C. for one hour, 85° C. for twohours and finally at 95° C. for seven hours. Stirring speed was set to280 rpm.

After polymerization was completed, the resulting cross-linked copolymerbeads were separated on sieves, washed with hot water, water andacetone, then preswollen in toluene and extracted with this solvent foreight hours using Soxhlet apparatus, and then dried. A subsequentnucleophilic reaction using a carbanion as nucleophile indicated thatabout 1.23 mmol of replaceable chloride per gram dry weight was presentin the beads.

Preparation B

Insoluble, cross-linked copolymer beads (70.7 g) were obtained bysuspension polymerization of 90.5 weight percent vinylbenzyl chloride,2.0 weight percent divinylbenzene, and 0.5 weight percent benzoylperoxide (with the ethylstyrenes present in the technical gradedivinylbenzene). A nucleophilic reaction with a carbanion nucleophileindicated the presence of about 1.62 mmol of replaceable chloride pergram dry weight of this resin.

Preparation C

Insoluble, cross-linked copolymer beads (100 g) were obtained bysuspension polymerization of 2.0 weight percent of2-ethyl-(2-hydroxymethyl)-1,3-propanediol trimethacrylate, 97 weightpercent of glycidyl methacrylate and 1.0 weight percent of benzoylperoxide. About 1.3 mmol per gram dry weight of ring-openable epoxidegroups were found upon nucleophilic reaction with a carbanion.

Dry Weight Conversion Factor

Weight conversion factors that are a measure of the wettability ofseparation particles and figure in D_(w) calculations are determined asfollows.

A sample of separation particles is hydrated in an excess of water for30 minutes at room temperature, and then filtered on a Buchner funneland dried in place with a stream of water-saturated air for 5 minutes ata pressure of about 660-670 torr. A portion of that air-dried materialis removed, weighed and then dried in an oven at 110° C. until aconstant mass was obtained. The dry mass of the separation particlesdivided by the mass of air-dried separation particles provided the dryweight conversion factor. Each gravimetric analysis was performed induplicate, and was repeated each time a new batch of hydrated separationparticles was prepared.

Separation Particle Loading Study

Distribution values for NH₄ TCO₄ were determined using 107-5000separation particles in 2.00M (2.31 m) (NH₄)₂ SO₄ solution at 25° C. inthe absence and presence of NH₄ ReO₄ at 10⁻⁵, 5×10⁻⁵, 10⁻⁴, 5×10⁻⁴ and10⁻³ molar concentrations. The data from these studies are shown in FIG.13. As is seen, there was little decrease in the observed D_(w) values,even at 10⁻³ M NH₄ ReO₄. This lack of decrease indicates that the TcO₄⁻¹ ions were not displaced by the ReO₄ ⁻¹ ions, and that the capacity ofthe separation particles is at least 10⁻³ molar TcO₄ ⁻¹ per gram ofparticles.

Weight Distribution and Percent CH₂ O/mm² Surface Area

D_(w) values were determined for TcO₄ ⁻¹ ions in 5.92 m K₂ CO₃ solutionusing 107-350, -750, -2000, -5000 and -5750 separation particlesprepared from 200-400 mesh Merrifield's peptide resin (polystyrene-1percent-divinylbenzene) precursor particles. The unreacted particleswere also assayed.

The results are shown in FIG. 14 plotted against the percent CH₂ O/mm²particle surface area. As is seen from the data, D_(w) values of about100 or more that indicate useful materials occur at CH₂ O/mm² valuesgreater than about 8000.

Radiolysis Stability Studies

Radiolysis studies were carried out to determine the stability of anillustrative batch of 107 separation particles to high doses of ionizingradiation. Approximately 500 mg samples of 107-5000 separation particlesin about 2 mL of water or 5M NaOH were put into glass culture tubes. Thetubes were placed into the 70,000 Ci ⁶⁰ Co γ-irradiation facility atArgonne National Laboratory and were subjected to doses ranging from 1.2Mrads/2 hours to 24 Mrads/40 hours. The irradiated samples were washedwith water, air dried and then weight distribution values (D_(w)) forTcO₄ ⁻¹ anions were determined at 25° C. to assay possible performancedegradation as a function of increasing radiation dose.

Up to 24 Mrads, D_(w) values showed no significant degradation ofperformance relative to an unirradiated sample of the same batch ofseparation particles through 4 m K₂ CO₃. Above that salt concentration,a decrease in D_(w) values was noted and not yet explained. However, theretention properties of the separation particles remained very high. Thesolvent variation from water to 5M NaOH during irradiation did notappear to alter the separation particles or adversely affect theiruptake properties.

The radiation doses used in these studies exceeded those anticipated inradiopharmaceutical waste separation applications and other presentlycontemplated uses by at least a factor of ten. The chemical andradiolytic stability and durability of the assayed separation particlesis evidenced by D_(w) values for TcO₄ ⁻¹ anions in the range of about10³ to about 10⁴ obtained after receiving a dose of 24 Mrads in anaqueous solution. Exemplary data for unirradiated separation particlesand separation particles irradiated with 1.2 Mrads and 24 Mrads in waterand 5M NaOH as well as separate particles irradiated with 12 Mrads inwater are shown in FIG. 15.

The foregoing description and the examples are intended as illustrativeand are not to be taken as limiting. Still other variations within thespirit and scope of this invention are possible and will readily presentthemselves to those skilled in the art.

We claim:
 1. A process for recovering TcO₄ ⁻¹ ions from an aqueoussolution that comprises the steps of:(a) contacting separation particleswith an aqueous solution containing (i) TcO₄ ⁻¹ ions and (ii) apoly(ethylene glycol) liquid/liquid biphase-forming amount of adissolved salt to form a solid/liquid phase admixture, said separationparticles comprising particles having a plurality of covalently bonded--X--(CH₂ CH₂ O)_(n) --CH₂ CH₂ R groups wherein X is O, S, NH or N--(CH₂CH₂ O)_(m) --R³ where m is a number having an average value of zero toabout 225, n is a number having an average value of about 15 to about225, R³ is hydrogen, C₁ -C₂ alkyl, 2-hydroxyethyl or CH₂ CH₂ R, and R isselected from the group consisting of --OH, C₁ -C₁₀ hydrocarbyl etherhaving a molecular weight up to about one-tenth that of the --(CH₂ CH₂O)_(n) -- portion, carboxylate, sulfonate, phosphonate and --NR¹ R²groups where each of R¹ and R² is independently hydrogen, C₂ -C₃hydroxyalkyl or C₁ -C₆ alkyl, or --NR¹ R² together form a 5- or6-membered cyclic amine having zero or one oxygen atom or zero or oneadditional nitrogen atom in the ring, said separation particles having apercent CH₂ O/mm² of particle surface area of greater than about 8000and less than about 1,000,000; (b) maintaining said contact for a timeperiod sufficient to form TcO₄ ⁻¹ ion-bound separation particles and anaqueous solution substantially free of TcO₄ ⁻¹ ions; (c) contacting saidTcO₄ ⁻¹ ion-bound separation particles with a second aqueous solutionthat does not contain a poly(ethylene glycol) liquid/liquidbiphase-forming amount of dissolved salt to free the TcO₄ ⁻¹ ions fromthe separation particles and form an aqueous solution containing freeTcO₄ ⁻¹ ions; and (d) recovering the TcO₄ ⁻¹ ion-containing aqueoussolution.
 2. The process according to claim 1 wherein the TcO₄ ⁻¹ is^(99m) TcO₄ ⁻¹.
 3. The process according to claim 1 including thefurther step of separating said TcO₄ ⁻¹ ion-bound separation particlesfrom the aqueous solution of step (b) in the presence of an aqueoussolution of a poly(ethylene glycol) liquid/liquid biphase-forming amountof a salt to form a second solid/liquid phase admixture containing TcO₄⁻¹ ion-bound separation particles.
 4. The process according to claim 1wherein n has an average value of about 40 to about
 130. 5. The processaccording to claim 1 wherein R is a C₁ -C₁₀ hydrocarbyl ether group. 6.The process according to claim 1 wherein said percent CH₂ O/mm² ofparticle surface area is about 9,000 to about 20,000.
 7. The processaccording to claim 1 wherein said particles are reacted cross-linkedpoly(styrene-vinyl benzyl halide) particles.
 8. The process according toclaim 1 wherein said aqueous solution of step (a) contains MoO₄ ⁻¹ ions.9. A process for recovering TcO₄ ⁻¹ ions from an aqueous solutioncontaining both TcO₄ ⁻¹ and MoO₄ ⁻² ions that comprises the steps of:(a)contacting separation particles with an aqueous solution containing (i)TcO₄ ⁻¹ ions, (ii) MoO₄ ⁻² ions and (iii) a poly(ethylene glycol)liquid/liquid biphase-forming amount of a dissolved salt whose anionscan include MoO₄ ⁻² ions to form a solid/liquid phase admixture, saidseparation particles comprising particles having a plurality ofcovalently bonded --X--(CH₂ CH₂ O)_(n) --CH₂ CH₂ R groups wherein X isS, O, NH or N--(CH₂ CH₂ O)_(m) --R³ where m is a number having anaverage value of zero to about 225, n is a number having an averagevalue of about 15 to about 225, R³ is hydrogen, C₁ -C₂ alkyl,2-hydroxyethyl or CH₂ CH₂ R, and R is selected from the group consistingof --OH, C₁ -C₁₀ hydrocarbyl ether having a molecular weight up to aboutone-tenth that of said (CH₂ CH₂ O)_(n) -portion, carboxylate, sulfonate,phosphonate and --NR¹ R² groups where each of R¹ and R² is independentlyhydrogen, C₁ -C₆ alkyl, or C₂ -C₃ hydroxyalkyl, or --NR¹ R² togetherform a 5- or 6-membered cyclic amine having zero or one oxygen atom orzero or one additional nitrogen atom in the ring, said separationparticles having a percent CH₂ O/mm² of particle surface area of greaterthan about 8000 and less than about 1,000,000; (b) maintaining saidcontact for a time period sufficient to form TcO₄ ⁻¹ ion-boundseparation particles and an aqueous solution substantially free of TcO₄⁻¹ ions; (c) separating said TcO₄ ⁻¹ ion-bound separation particles fromthe aqueous solution of step (b) in the presence of an aqueous solutionof a poly (ethylene glycol) liquid/liquid biphase-forming amount of saltfree of MoO₄ ⁻² ions to form a second solid/liquid phase admixturecontaining TcO₄ ⁻¹ ion-bound separation particles; (d) contacting saidTcO₄ ⁻¹ ion-bound separation particles of step (c) with a second aqueoussolution that does not contain a poly(ethylene glycol) liquid/liquidbiphase-forming amount of dissolved salt to free the TcO₄ ⁻ ions fromthe separation particles and form an aqueous solution containing freeTcO₄ ⁻¹ ions; and (e) recovering the TcO₄ ⁻¹ ion-containing aqueoussolution.
 10. The process according to claim 9 wherein the TcO₄ ⁻¹ is^(99m) TcO₄ ⁻¹ and the MoO₄ ⁻² is ⁹⁹ MoO₄ ⁻².
 11. The process accordingto claim 9 wherein n has an average value of about 40 to
 130. 12. Theprocess according to claim 9 wherein R is a C₁ -C₁₀ hydrocarbyl ethergroup.
 13. The process according to claim 9 wherein R is a C₁ -C₁₀hydrocarbyl ether group that is methoxy.
 14. The process according toclaim 9 wherein said percent CH₂ O/mm² of particle surface area is about9,000 to about 20,000.
 15. The process according to claim 9 wherein saidparticles are reacted cross-linked poly(styrenevinyl benzyl halide)particles.
 16. The process according to claim 9 wherein both radioactiveand non-radioactive MoO₄ ⁻² ions are present.
 17. A process forrecovering TcO₄ ⁻¹ ions from an aqueous solution containing both TcO₄ ⁻¹and radioactive MoO₄ ⁻² ions that comprises the steps of:(a) contactingseparation particles with an aqueous solution containing (i) TcO₄ ⁻¹ions, (ii) radioactive MoO₄ ⁻² ions and-(iii) a poly(ethylene glycol)liquid/liquid biphase-forming amount of a dissolved salt whose on ionscan include MoO₄ ⁻² ions to form a solid/liquid phase admixture, saidseparation particles comprising particles having a plurality ofcovalently bonded --X--(CH₂ CH₂ O)_(n) --CH₂ CH₂ R groups wherein X isS, O, NH or N--(CH₂ CH₂ O)_(m) --R³ wherein m is a number having anaverage value of zero to about 225, n is a number having an averagevalue of about 40 to about 130, R³ is hydrogen, C₁ -C₂ alkyl,2-hydroxyethyl or CH₂ CH₂ R, and R is selected from the group consistingof --OH, C₁ -C₁₀ hydrocarbyl ether having a molecular weight up to aboutone-tenth that of said (CH₂ CH₂ O)_(n) -portion, carboxylate, sulfonate,phosphonate and --NR¹ R² is independently hydrogen, C₁ -C₆ alkyl, or C₂-C₃ hydroxyalkyl, or --NR¹ R² groups where each of R¹ and R² togetherform a 5- or 6-membered cyclic amine having zero or one oxygen atom orzero or one additional nitrogen atom in the ring, said separationparticles having a percent CH₂ O/mm² of particle surface area of greaterthan about 9,000 and less than about 20,000; (b) maintaining saidcontact for a time period sufficient to form TcO₄ ⁻¹ ion-boundseparation particles and an aqueous solution substantially free of TcO₄⁻¹ ions; (c) separating said TcO₄ ⁻¹ ion-bound separation particles fromthe aqueous solution of step (b) in the presence of an aqueous solutionof a poly(ethylene glycol) liquid/liquid biphase-forming amount of saltfree of MoO₄ ⁻² ions to form a second solid/liquid phase admixturecontaining TcO₄ ⁻¹ ion-bound separation particles; (d) contacting saidTcO₄ ⁻¹ ion-bound separation particles of step (c) with a second aqueoussolution that does not contain a poly(ethylene glycol) liquid/liquidbiphase-forming amount of dissolved salt to free the TcO₄ ⁻¹ ions fromthe separation particles and form an aqueous solution containing freeradioactive TcO₄ ⁻¹ ions; and (e) recovering the TcO₄ ⁻¹ ion-containingaqueous solution.
 18. The process according to claim 17 wherein the TcO₄⁻¹ is ^(99m) TcO₄ ⁻¹ and the radioactive MoO₄ ⁻² is ⁹⁹ MoO₄ ⁻².
 19. Theprocess according to claim 18 wherein non-radioactive MoO₄ ⁻² ions arealso present.
 20. The process according to claim 17 wherein saidparticles are reacted cross-linked poly(styrene-vinyl benzyl halide)particles.
 21. A chromatography apparatus comprising a chromatographycolumn containing an aqueous solution and a plurality of separationparticles bound to TcO₄ ⁻¹ ions, said aqueous solution containing apoly(ethylene glycol) liquid/liquid biphase-forming amount of adissolved salt free of MoO₄ ⁻² ions, said separation particlescomprising particles having a plurality of covalently bonded surface--X--(CH₂ CH₂ O)_(n) --CH₂ CH₂ R groups wherein X is S, O, NH or N--(CH₂CH₂ O)_(m) --R wherein m is a number having an average value of zero toabout 225, n is a number having an average value of about 15 to about225, R³ is hydrogen, C₁ -C₂ alkyl, 2-hydroxyethyl, or CH₂ CH₂ R, and Ris selected from the group consisting of --OH, C₁ -C₁₀ hydrocarbyl etherhaving a molecular weight up to about one-tenth that of said --(CH₂ CH₂O)_(n) portion, carboxylate, sulfonate, phosphonate and --NR¹ R² groupswhere each of R¹ and R² is independently hydrogen, C₁ -C₆ alkyl or C₂-C₃ hydroxyalkyl, or --NR¹ R² together form a 5- or 6-membered cyclicamine having zero or one oxygen atom or zero or one additional nitrogenatom in the ring, said separation particles having a percent CH₂ O/mm²of particle surface area of greater than about 8000 and less than about1,000,000.
 22. The chromatography apparatus according to claim 21wherein the TcO₄ ⁻¹ is ^(99m) TcO₄ ⁻¹.
 23. The chromatography apparatusaccording to claim 21 wherein n has an average value of about 40 toabout
 130. 24. The chromatography apparatus according to claim 21wherein R is a C₁ -C₁₀ hydrocarbyl ether group.
 25. The chromatographyapparatus according to claim 21 wherein said percent CH₂ O/mm² ofparticle surface area is about 9,000 to about 20,000.
 26. Thechromatography apparatus according to claim 21 wherein said separationparticles are reacted cross-linked poly(styrene-vinyl benzyl halide)particles.
 27. A solid/liquid phase admixture comprising TcO₄ ⁻¹ion-bound separation particles as the solid phase in an aqueous solutionof a poly(ethylene glycol) liquid/liqUid biphase-forming amount of adissolved salt that is free of MoO₄ ⁻² ions, said separation particlescomprising particles having a plurality of covalently bonded surface--X--(CH₂ CH₂ O)_(n) --CH₂ CH₂ R groups wherein X is S, O, NH or N--(CH₂CH₂ O)_(m) --R wherein m is a number having an average value of zero toabout 225, n is a number having an average value of about 15 to about225, R³ is hydrogen, C₁ -C₂ alkyl, 2-hydroxyethyl, or CH₂ CH₂ R, and Ris selected from the group consisting of --OH, C₁ -C₁₀ hydrocarbyl etherhaving a molecular weight up to about one-tenth that of said --(CH₂ CH₂O)_(n) -- portion, carboxylate, sulfonate, phosphonate and --NR¹ R²groups where each of R¹ and R² is independently hydrogen, C₁ -C₆ alkylor C₂ -C₃ hydroxyalkyl, or --NR¹ R² together form a 5- or 6-memberedcyclic amine having zero or one oxygen atom or zero or one additionalnitrogen atom in the ring, said separation particles having a percentCH₂ O/mm² of particle surface area of greater than about 8000 and lessthan about 1,000,000.
 28. The solid/liquid phase admixture according toclaim 27 wherein the TcO₄ ⁻¹ is ^(99m) TcO₄ ⁻¹.
 29. The solid/liquidphase admixture according to claim 27 wherein n has an average value ofabout 40 to about
 130. 30. The solid/liquid phase admixture according toclaim 27 wherein R is a C₁ -C₁₀ hydrocarbyl ether group.
 31. Thesolid/liquid phase admixture according to claim 27 wherein said percentCH₂ O/mm² of particle surface area is about 9,000 to about 20,000.